DGIdb - KRAS Gene Record

KRAS 3845 Clinically ActionableDrug Resistance

Alternate Names:

3845
KRAS PROTO-ONCOGENE, GTPASE
KRAS
C-K-RAS
CFC2
K-RAS2A
K-RAS2B
K-RAS4A
K-RAS4B
K-Ras
KI-RAS
KRAS1
KRAS2
NS
NS3
RALD
RASK2
c-Ki-ras2
190070
6407
ENSG00000133703
OTTHUMG00000171193
PA30196
3485
2824
P01116
30
BE0004071
GTPase KRas
T48598
NM_004985\|NM_033360
NP_004976\|NP_203524

Gene Info:

CancerCommons Reported Gene Name	KRAS-RAS
Target Class	Miscellaneous
Target Subclass	Miscellaneous
Target Subclass	Hras
Gene Biotype	PROTEIN_CODING
GuideToPharmacology Gene Category Name	RAS subfamily
GuideToPharmacology Gene Category ID	897

(16 More Sources)

Gene Categories: Category Details

KINASE
SERINE THREONINE KINASE
DRUG RESISTANCE
CLINICALLY ACTIONABLE
ENZYME

Publications:

Roper et al., 2014, Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer., Cancer Lett.
Vansteenkiste et al., 2015, Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study., J Thorac Oncol
Hong et al., 2016, Targeting the PI3K signaling pathway in KRAS mutant colon cancer., Cancer Med
Park et al., 2012, NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations., Int. J. Oncol.
Gerdes et al., 2013, GA201 (RG7160): a novel, humanized, glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab., Clin. Cancer Res.
Bertino et al., 2016, A Phase I Trial to Evaluate Antibody-Dependent Cellular Cytotoxicity of Cetuximab and Lenalidomide in Advanced Colorectal and Head and Neck Cancer., Mol. Cancer Ther.
Hatzivassiliou et al., 2013, Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers., Nature
Hoeflich et al., 2012, Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition., Cancer Res.
Papadimitrakopoulou et al., 2016, The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer., J. Clin. Oncol.
Hu et al., 2015, Combined Inhibition of Cyclin-Dependent Kinases (Dinaciclib) and AKT (MK-2206) Blocks Pancreatic Tumor Growth and Metastases in Patient-Derived Xenograft Models., Mol. Cancer Ther.
Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
Yap et al., 2011, First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors., J. Clin. Oncol.
Riquelme et al., 2016, Modulation of EZH2 Expression by MEK-ERK or PI3K-AKT Signaling in Lung Cancer Is Dictated by Different KRAS Oncogene Mutations., Cancer Res.
Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.
Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.
Pao et al., 2005, KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib., PLoS Med.
Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature
Ludovini V et al., 2011, Phosphoinositide-3-kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer., J Thorac Oncol
Marchetti et al., 2009, Clinical implications of KRAS mutations in lung cancer patients treated with tyrosine kinase inhibitors: an important role for mutations in minor clones., Neoplasia
Fiala et al., The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer., Cancer Genet
Kim et al., 2017, Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review., Oncotarget
Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer
Paz-Ares et al., 2015, Monotherapy Administration of Sorafenib in Patients With Non-Small Cell Lung Cancer (MISSION) Trial: A Phase III, Multicenter, Placebo-Controlled Trial of Sorafenib in Patients with Relapsed or Refractory Predominantly Nonsquamous Non-Small-Cell Lung Cancer after 2 or 3 Previous Treatment Regimens., J Thorac Oncol
Dingemans et al., 2013, A phase II study of sorafenib in patients with platinum-pretreated, advanced (Stage IIIb or IV) non-small cell lung cancer with a KRAS mutation., Clin. Cancer Res.
Wilson et al., 2016, Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma., Clin. Cancer Res.
Lim et al., 2014, A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma., Clin. Cancer Res.
Falchook et al., 2015, Dual antiangiogenic inhibition: a phase I dose escalation and expansion trial targeting VEGF-A and VEGFR in patients with advanced solid tumors., Invest New Drugs
Gandara et al., 2017, A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer., J Thorac Oncol
Sun et al., 2014, Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3., Cell Rep
Jing et al., 2012, Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212., Mol. Cancer Ther.
Infante et al., 2014, A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas., Eur. J. Cancer
Ball et al., 2015, Trametinib with and without pazopanib has potent preclinical activity in thyroid cancer., Oncol. Rep.
Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.
Gannon et al., 2016, Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy., Mol. Cancer Res.
Yamaguchi et al., 2016, A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers., Oncotarget
Brammeld et al., 2017, Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations., Genome Res.
Lin et al., 2015, The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies., Nat. Genet.
Infante et al., 2012, Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial., Lancet Oncol.
Dhawan et al., 2016, Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling., Nature
Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell
Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.
Ziemke et al., 2016, Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy That Cotargets MEK and CDK4/6., Clin. Cancer Res.
Russo et al., 2016, Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer., Cancer Discov
Li et al., 2013, The AKT inhibitor AZD5363 is selectively active in PI3KCA mutant gastric cancer, and sensitizes a patient-derived gastric cancer xenograft model with PTEN loss to Taxotere., J Transl Med
Yoon et al., 2009, Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells., Mol. Cancer Ther.
De Roock et al., 2010, Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab., JAMA
Janssen et al., 1987, RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes., Proc. Natl. Acad. Sci. U.S.A.
Lee et al., 2011, Effect of simvastatin on cetuximab resistance in human colorectal cancer with KRAS mutations., J. Natl. Cancer Inst.
Neumann et al., 2009, Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer., Pathol. Res. Pract.
Amado et al., 2008, Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer., J. Clin. Oncol.
Tyner et al., 2009, High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients., Blood
Peeters et al., 2013, Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab., J. Clin. Oncol.
Haldar et al., 2011, Epidermal growth factor receptor blockers for the treatment of ovarian cancer., Cochrane Database Syst Rev
Rowland et al., 2016, Meta-analysis comparing the efficacy of anti-EGFR monoclonal antibody therapy between KRAS G13D and other KRAS mutant metastatic colorectal cancer tumours., Eur. J. Cancer
Nakayama et al., 2008, KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer., Br. J. Cancer
Ho et al., 2013, Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer., N. Engl. J. Med.
Tejpar et al., 2012, Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab., J. Clin. Oncol.
Bokemeyer et al., 2009, Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer., J. Clin. Oncol.
Lièvre et al., 2006, KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer., Cancer Res.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Bokemeyer et al., 2011, Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study., Ann. Oncol.
Schubbert et al., 2007, Hyperactive Ras in developmental disorders and cancer., Nat. Rev. Cancer
Kloos et al., 2009, Phase II trial of sorafenib in metastatic thyroid cancer., J. Clin. Oncol.
Schirripa et al., 2015, Phase II study of single-agent cetuximab in KRAS G13D mutant metastatic colorectal cancer., Ann. Oncol.
Peeters et al., 2010, Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer., J. Clin. Oncol.
Riely et al., 2008, Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma., Clin. Cancer Res.
Bacher et al., 2006, Implications of NRAS mutations in AML: a study of 2502 patients., Blood
Hoftijzer et al., 2009, Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma., Eur. J. Endocrinol.
Migliardi et al., 2012, Inhibition of MEK and PI3K/mTOR suppresses tumor growth but does not cause tumor regression in patient-derived xenografts of RAS-mutant colorectal carcinomas., Clin. Cancer Res.
Rothenberg et al., 2005, Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma., J. Clin. Oncol.
Osumi et al., 2015, Cetuximab treatment for metastatic colorectal cancer with KRAS p.G13D mutations improves progression-free survival., Mol Clin Oncol
Sano et al., 2012, RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse: a study of the Japanese Childhood AML Cooperative Study Group., Int. J. Hematol.
Kumar et al., 2014, KRAS G13D Mutation and Sensitivity to Cetuximab or Panitumumab in a Colorectal Cancer Cell Line Model., Gastrointest Cancer Res
Douillard et al., 2010, Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study., J. Clin. Oncol.
Brose et al., 2002, BRAF and RAS mutations in human lung cancer and melanoma., Cancer Res.
Vogelstein et al., 1990, RAS gene mutations in childhood acute myeloid leukemia: a Pediatric Oncology Group study., Genes Chromosomes Cancer
Janakiraman et al., 2010, Genomic and biological characterization of exon 4 KRAS mutations in human cancer., Cancer Res.
Parseghian et al., 2017, Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined with FOLFOX Chemotherapy in Patients with Metastatic Colorectal Cancer., Clin. Cancer Res.
Venook et al., 2017, Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial., JAMA
Ramos et al., 2008, Understanding the predictive role of K-ras for epidermal growth factor receptor-targeted therapies in colorectal cancer., Clin Colorectal Cancer
Hechtman et al., 2015, AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants., Mol. Cancer Res.
Ciardiello et al., 2016, Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX., Ann. Oncol.
Osumi et al., 2013, Acquired drug resistance conferred by a KRAS gene mutation following the administration of cetuximab: a case report., BMC Res Notes
Van Cutsem et al., 2015, Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer., J. Clin. Oncol.
Napolitano et al., 2015, Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab., Clin. Cancer Res.
Lièvre et al., 2008, KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab., J. Clin. Oncol.
Pirazzoli et al., 2016, Afatinib plus Cetuximab Delays Resistance Compared to Single-Agent Erlotinib or Afatinib in Mouse Models of TKI-Naïve EGFR L858R-Induced Lung Adenocarcinoma., Clin. Cancer Res.
Deming et al., 2016, A phase I study of selumetinib (AZD6244/ARRY-142866), a MEK1/2 inhibitor, in combination with cetuximab in refractory solid tumors and KRAS mutant colorectal cancer., Invest New Drugs
Morgen EK et al., 2017, Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis., Pharmacogenomics J
Allegra CJ et al., 2016, Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015., J Clin Oncol
Sclafani F et al., 2015, Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial., Ann Oncol
Ying HQ et al., 2014, The involvement of Kras gene 3'-UTR polymorphisms in risk of cancer and influence on patient response to anti-EGFR therapy in metastatic colorectal cancer: a meta-analysis., Onco Targets Ther
Saridaki Z et al., 2014, A let-7 microRNA-binding site polymorphism in KRAS predicts improved outcome in patients with metastatic colorectal cancer treated with salvage cetuximab/panitumumab monotherapy., Clin Cancer Res
Sha D et al., 2014, Association study of the let-7 miRNA-complementary site variant in the 3' untranslated region of the KRAS gene in stage III colon cancer (NCCTG N0147 Clinical Trial)., Clin Cancer Res
Sebio A et al., 2013, The LCS6 polymorphism in the binding site of let-7 microRNA to the KRAS 3'-untranslated region: its role in the efficacy of anti-EGFR-based therapy in metastatic colorectal cancer patients., Pharmacogenet Genomics
Chen J et al., 2013, Association between KRAS codon 13 mutations and clinical response to anti-EGFR treatment in patients with metastatic colorectal cancer: results from a meta-analysis., Cancer Chemother Pharmacol
Bando H et al., 2012, Clinical outcome of Japanese metastatic colorectal cancer patients harbouring the KRAS p.G13D mutation treated with cetuximab + irinotecan., Jpn J Clin Oncol
Gajate P et al., 2012, Influence of KRAS p.G13D mutation in patients with metastatic colorectal cancer treated with cetuximab., Clin Colorectal Cancer
Kaczirek et al., 2015, FOLFOX4 Plus Cetuximab for Patients With Previously Untreated Metastatic Colorectal Cancer According to Tumor RAS and BRAF Mutation Status: Updated Analysis of the CECOG/CORE 1.2.002 Study., Clin Colorectal Cancer
Loupakis et al., 2009, KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer., Br. J. Cancer
Misale et al., 2012, Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer., Nature
Benson et al., 2017, Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology., J Natl Compr Canc Netw
Bertotti et al., 2011, A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer., Cancer Discov
Dunn et al., 2011, Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab., Oncogene
Sartore-Bianchi et al., 2009, PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies., Cancer Res.
Souglakos J et al., 2009, Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer., Br J Cancer
De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.
Karapetis et al., 2008, K-ras mutations and benefit from cetuximab in advanced colorectal cancer., N. Engl. J. Med.
Sato N et al., 2012, Cetuximab inhibits the growth of mucinous ovarian carcinoma tumor cells lacking KRAS gene mutations., Oncol Rep
Valtorta E et al., 2013, KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy., Int J Cancer
Ahronian et al., 2015, Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations., Cancer Discov
French D et al., 2011, KRAS mutation detection in colorectal cancer by a commercially available gene chip array compares well with Sanger sequencing., Clin Chim Acta
Sartore-Bianchi et al., 2016, Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial., Lancet Oncol.
Lou et al., 2017, Therapeutic Response of Metastatic Colorectal Cancer Harboring a KRAS Missense Mutation After Combination Chemotherapy With the EGFR Inhibitor Panitumumab., J Natl Compr Canc Netw
Leone et al., 2016, Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study)., Cancer
Poulin-Costello et al., 2013, An analysis of the treatment effect of panitumumab on overall survival from a phase 3, randomized, controlled, multicenter trial (20020408) in patients with chemotherapy refractory metastatic colorectal cancer., Target Oncol
Van Cutsem et al., 2014, Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer., Clin. Cancer Res.
Peeters et al., 2015, Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer., Clin. Cancer Res.
Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
Nakanishi et al., 2015, ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor., Mol. Cancer Ther.
Takekuma et al., 2016, A long-term surviving patient with recurrent low-grade serous ovarian carcinoma treated with the MEK1/2 inhibitor, selumetinib., Gynecol Oncol Res Pract
Whittaker et al., 2015, Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors., Mol. Cancer Ther.
Jänne et al., 2015, Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer., Br. J. Cancer
Qian et al., 2014, Whole genome gene copy number profiling of gastric cancer identifies PAK1 and KRAS gene amplification as therapy targets., Genes Chromosomes Cancer
Jänne et al., 2013, Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study., Lancet Oncol.
Jänne et al., 2017, Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial., JAMA
McNew et al., 2016, MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling., Mol. Cancer Res.
Qu et al., 2014, Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft models., J. Exp. Clin. Cancer Res.
Holt et al., 2012, Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055)., Cancer Res.
Engelman et al., 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers., Nat. Med.
Hofmann et al., 2012, K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo., PLoS ONE
García-García et al., 2015, MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer., Clin. Cancer Res.
Depreeuw et al., 2015, Characterization of patient-derived tumor xenograft models of endometrial cancer for preclinical evaluation of targeted therapies., Gynecol. Oncol.
Kim et al., 2016, Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS-Mutant Lung Cancer., Mol. Cancer Res.
Hochster et al., 2015, Phase II study of selumetinib (AZD6244, ARRY-142886) plus irinotecan as second-line therapy in patients with K-RAS mutated colorectal cancer., Cancer Chemother. Pharmacol.
Ebi et al., 2011, Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers., J. Clin. Invest.
Lamba et al., 2014, RAF suppression synergizes with MEK inhibition in KRAS mutant cancer cells., Cell Rep
Ross et al., 2017, Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS., Sci Transl Med
Yu et al., 2014, Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathway., Mol. Cancer Ther.
Mallon et al., 2010, Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor., Mol. Cancer Ther.
Brugger et al., 2011, Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer., J. Clin. Oncol.
Kim et al., 2011, Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients treated with first-line gemcitabine-based chemotherapy., Mol. Cancer Ther.
Zhu et al., 2008, Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21., J. Clin. Oncol.
Eberhard et al., 2005, Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib., J. Clin. Oncol.
Chung et al., 2014, A 3'-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma., Ann. Oncol.
Kang et al., 2016, ER2, a novel human anti-EGFR monoclonal antibody inhibit tumor activity in non-small cell lung cancer models., Lung Cancer
Richer et al., 2017, WEE1 Kinase Inhibitor AZD1775 Has Preclinical Efficacy in LKB1-Deficient Non-Small Cell Lung Cancer., Cancer Res.
Wilhelm et al., 2011, Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity., Int. J. Cancer
Loaiza-Bonilla et al., 2016, KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer., Cureus
Saha et al., 2016, Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma., Cancer Discov
Maitra et al., 2014, Oncolytic reovirus preferentially induces apoptosis in KRAS mutant colorectal cancer cells, and synergizes with irinotecan., Oncotarget
Mahalingam et al., 2015, The combination of intravenous Reolysin and gemcitabine induces reovirus replication and endoplasmic reticular stress in a patient with KRAS-activated pancreatic cancer., BMC Cancer
Danilov et al., 2016, Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2., Mol. Cancer Ther.
Ahmed et al., 2013, Epigenetic and genetic features of 24 colon cancer cell lines., Oncogenesis
Smakman et al., 2006, KRAS(D13) Promotes apoptosis of human colorectal tumor cells by ReovirusT3D and oxaliplatin but not by tumor necrosis factor-related apoptosis-inducing ligand., Cancer Res.
Mallon et al., 2011, Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor., Clin. Cancer Res.
Canon et al., 2015, The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates the Activity of p53-Inducing Cytotoxic Agents., Mol. Cancer Ther.
Ortiz-Cuaran et al., 2016, Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors., Clin. Cancer Res.
Kumar et al., 2012, The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer., Cell
Schmitt et al., 2017, ATM Deficiency Is Associated with Sensitivity to PARP1- and ATR Inhibitors in Lung Adenocarcinoma., Cancer Res.
Patnaik et al., 2016, Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors., Cancer Discov
Glover et al., 1992, Gastroenteritis outbreak at an industrial camp--British Columbia., Can. Commun. Dis. Rep.
Sherr et al., 2016, Targeting CDK4 and CDK6: From Discovery to Therapy., Cancer Discov
Montero et al., 2016, A Phase I Clinical, Pharmacokinetic, and Pharmacodynamic Study of Weekly or Every Three Week Ixabepilone and Daily Sunitinib in Patients with Advanced Solid Tumors., Clin. Cancer Res.
Modest et al., 2013, KRAS allel-specific activity of sunitinib in an isogenic disease model of colorectal cancer., J. Cancer Res. Clin. Oncol.
Soares et al., 2015, Dual PI3K/mTOR Inhibitors Induce Rapid Overactivation of the MEK/ERK Pathway in Human Pancreatic Cancer Cells through Suppression of mTORC2., Mol. Cancer Ther.
Wallin et al., 2011, GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway., Mol. Cancer Ther.
Liu et al., 2013, BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models., Mol. Cancer Ther.
Fernandes MS et al., 2016 Oct 18, Specific inhibition of p110α subunit of PI3K: putative therapeutic strategy for KRAS mutant colorectal cancers., Oncotarget
Fritsch et al., 2014, Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials., Mol. Cancer Ther.
Anderson et al., 2016, PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation., Sci Transl Med
Tabernero et al., 2015, Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study., Lancet Oncol.
Lee et al., 2016, Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models., Oncotarget
Hamidi et al., 2014, KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition., Br. J. Cancer
Bendell et al., 2017, A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor., Br. J. Cancer
Raja et al., 2015, Assessment of the In Vivo Activity of PI3K and MEK Inhibitors in Genetically Defined Models of Colorectal Cancer., Mol. Cancer Ther.
Monk BJ et al., 2020, MILO/ENGOT-ov11: Binimetinib Versus Physician's Choice Chemotherapy in Recurrent or Persistent Low-Grade Serous Carcinomas of the Ovary, Fallopian Tube, or Primary Peritoneum., J Clin Oncol
Qian et al., 2012, Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling., Clin. Cancer Res.
Scholl et al., 2009, Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells., Cell
Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.
Myers et al., 2016, Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology Group study., Gynecol. Oncol.
Lin et al., 2012, KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells., PLoS ONE
Raats et al., 2011, Synergistic killing of colorectal cancer cells by oxaliplatin and ABT-737., Cell Oncol (Dordr)
Elez et al., 2016, Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer., Br. J. Cancer
Momcilovic et al., 2015, Heightening Energetic Stress Selectively Targets LKB1-Deficient Non-Small Cell Lung Cancers., Cancer Res.
Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov
Shoji et al., 2012, Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas., PLoS ONE
Di Nicolantonio et al., 2010, Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus., J. Clin. Invest.
Mohseni et al., 2010, PIK3CA and KRAS mutations predict for response to everolimus therapy: now that's RAD001., J. Clin. Invest.
Gálvez-Peralta et al., 2014, Context-dependent antagonism between Akt inhibitors and topoisomerase poisons., Mol. Pharmacol.
Dumble et al., 2014, Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor., PLoS ONE
Egile et al., 2015, The selective intravenous inhibitor of the MET tyrosine kinase SAR125844 inhibits tumor growth in MET-amplified cancer., Mol. Cancer Ther.
Van Laethem et al., 2017, Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer., Target Oncol
O'Neil et al., 2015, A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer., Ann. Oncol.
Osborne et al., 2016, Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737)., J. Med. Chem.
Vena et al., 2015, The MEK1/2 Inhibitor Pimasertib Enhances Gemcitabine Efficacy in Pancreatic Cancer Models by Altering Ribonucleotide Reductase Subunit-1 (RRM1)., Clin. Cancer Res.
Juric et al., 2017, Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors., Cancer Discov
Yap et al., 2012, AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity., Clin. Cancer Res.
Hudson et al., 2016, Intermittent High-Dose Scheduling of AZD8835, a Novel Selective Inhibitor of PI3Kα and PI3Kδ, Demonstrates Treatment Strategies for PIK3CA-Dependent Breast Cancers., Mol. Cancer Ther.
Leijen et al., 2016, Phase II Study of WEE1 Inhibitor AZD1775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line Therapy Within 3 Months., J. Clin. Oncol.
Foster et al., 2015, The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models., Mol. Cancer Ther.
Ratner et al., 2012, A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer., Oncogene
Yeh et al., 2009, KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer., Mol. Cancer Ther.
Kim et al., 2013, Coexistent mutations of KRAS and PIK3CA affect the efficacy of NVP-BEZ235, a dual PI3K/MTOR inhibitor, in regulating the PI3K/MTOR pathway in colorectal cancer., Int. J. Cancer
Riely et al., 2011, A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS mutations., J Thorac Oncol
Laheru D et al., 2012, Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic Acid (FTS, Salirasib) in pancreatic cancer., Invest New Drugs
Yuan et al., 2011, PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity., Mol. Cancer Ther.
Mortensen et al., 2015, CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization., Mol. Cancer Ther.
Athuluri-Divakar et al., 2016, A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling., Cell
Weisberg et al., 2015, Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies., Leukemia
Mahoney et al., 2009, LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition., Br. J. Cancer
Ambrogio et al., 2016, Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma., Nat. Med.
Sherman et al., 2016, Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer., Cancer
Bhagwat et al., 2011, Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin., Mol. Cancer Ther.
Dong et al., 2017, Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma., Clin. Cancer Res.
Chen et al., 2017, KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung adenocarcinoma., Cancer Immunol. Immunother.
Dietlein et al., 2015, A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer., Cell
Ferrarotto et al., 2016, Epithelial-Mesenchymal Transition Predicts Polo-Like Kinase 1 Inhibitor-Mediated Apoptosis in Non-Small Cell Lung Cancer., Clin. Cancer Res.
Kashiyama et al., 2014, Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423., PLoS ONE
Petrelli et al., 2013, KRAS as prognostic biomarker in metastatic colorectal cancer patients treated with bevacizumab: a pooled analysis of 12 published trials., Med. Oncol.
Palm et al., 2015, The Utilization of Extracellular Proteins as Nutrients Is Suppressed by mTORC1., Cell
Perera et al., 2017, Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor., Mol. Cancer Ther.
Yang et al., 2008, Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer., PLoS ONE
Ma et al., 2013, K‑ras gene mutation as a predictor of cancer cell responsiveness to metformin., Mol Med Rep
Iglesias et al., 2013, Another surprise from Metformin: novel mechanism of action via K-Ras influences endometrial cancer response to therapy., Mol. Cancer Ther.
Xie J et al., 2020, Metformin selectively inhibits metastatic colorectal cancer with the <i>KRAS</i> mutation by intracellular accumulation through silencing MATE1., Proc Natl Acad Sci U S A
Song et al., 2015, Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer., Clin. Cancer Res.
Zimmer et al., 2014, Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations., Clin. Cancer Res.
Stewart et al., 2015, KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine., Cancer Res.
Hunter et al., 2015, Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations., Mol. Cancer Res.
Boasberg et al., 2011, Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer., Cancer Chemother. Pharmacol.
Simmons et al., 2012, Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras(G12D-LSL) mice., Cancer Chemother. Pharmacol.
Lee et al., 2010, Deguelin promotes apoptosis and inhibits angiogenesis of gastric cancer., Oncol. Rep.
Nam et al., 2011, Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer., Cancer Lett.
Hollestelle et al., 2007, Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines., Mol. Cancer Res.
Acquaviva et al., 2012, Targeting KRAS-mutant non-small cell lung cancer with the Hsp90 inhibitor ganetespib., Mol. Cancer Ther.
Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature
Palma et al., 2014, Durable Response to Crizotinib in a MET-Amplified, KRAS-Mutated Carcinoma of Unknown Primary., Case Rep Oncol
Kwak et al., 2015, Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer., Cancer Discov
Lieu et al., 2015, Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts., Oncotarget
Tanaka et al., 2011, The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations., Clin. Cancer Res.
Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

SELUMETINIB KRAS

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Osimertinib + Selumetinib

Indication/Tumor Type thyroid cancer

combination therapy Dasatinib + Selumetinib

Publications:

Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

Nakanishi et al., 2015, ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor., Mol. Cancer Ther.

REGORAFENIB KRAS

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family Pan-kinase inhibitor

Alteration KRAS:.

Indication/Tumor Type breast cancer

Publications:

Wilhelm et al., 2011, Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity., Int. J. Cancer

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

Loaiza-Bonilla et al., 2016, KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer., Cureus

PELAREOREP KRAS

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Reolysin + Gemcitabine

Indication/Tumor Type pancreatic cancer

Response Type sensitive

Publications:

Maitra et al., 2014, Oncolytic reovirus preferentially induces apoptosis in KRAS mutant colorectal cancer cells, and synergizes with irinotecan., Oncotarget

Mahalingam et al., 2015, The combination of intravenous Reolysin and gemcitabine induces reovirus replication and endoplasmic reticular stress in a patient with KRAS-activated pancreatic cancer., BMC Cancer

LONAFARNIB KRAS

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:

BUPARLISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BKM120 + AG490

Indication/Tumor Type stomach cancer

Response Type sensitive

Publications:

Roper et al., 2014, Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer., Cancer Lett.

Vansteenkiste et al., 2015, Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study., J Thorac Oncol

Hong et al., 2016, Targeting the PI3K signaling pathway in KRAS mutant colon cancer., Cancer Med

IMGATUZUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Gerdes et al., 2013, GA201 (RG7160): a novel, humanized, glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab., Clin. Cancer Res.
LENALIDOMIDE KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + lenalidomide

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:

Bertino et al., 2016, A Phase I Trial to Evaluate Antibody-Dependent Cellular Cytotoxicity of Cetuximab and Lenalidomide in Advanced Colorectal and Head and Neck Cancer., Mol. Cancer Ther.

COBIMETINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Atezolizumab + Cobimetinib

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:

Hatzivassiliou et al., 2013, Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers., Nature

Hoeflich et al., 2012, Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition., Cancer Res.

MK-2206 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy DZNep + MK2206

Indication/Tumor Type pancreatic cancer

Response Type sensitive

Publications:

Papadimitrakopoulou et al., 2016, The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer., J. Clin. Oncol.

Hu et al., 2015, Combined Inhibition of Cyclin-Dependent Kinases (Dinaciclib) and AKT (MK-2206) Blocks Pancreatic Tumor Growth and Metastases in Patient-Derived Xenograft Models., Mol. Cancer Ther.

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

CGM-097 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + Alpelisib + CGM097 + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.

GEFITINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Gefitinib + Trametinib

Indication/Tumor Type lung cancer

Response Type no benefit

Publications:

Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.

Pao et al., 2005, KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib., PLoS Med.

Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature

SORAFENIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Alteration KRAS:.

Drug family Pan-TK inhibitor;MEK inhibitor

combination therapy Sorafenib;MEK inhibitor

Publications:

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

Paz-Ares et al., 2015, Monotherapy Administration of Sorafenib in Patients With Non-Small Cell Lung Cancer (MISSION) Trial: A Phase III, Multicenter, Placebo-Controlled Trial of Sorafenib in Patients with Relapsed or Refractory Predominantly Nonsquamous Non-Small-Cell Lung Cancer after 2 or 3 Previous Treatment Regimens., J Thorac Oncol

Dingemans et al., 2013, A phase II study of sorafenib in patients with platinum-pretreated, advanced (Stage IIIb or IV) non-small cell lung cancer with a KRAS mutation., Clin. Cancer Res.

TRAMETINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pazopanib + Trametinib

Indication/Tumor Type thyroid cancer

combination therapy Dasatinib + Trametinib

Publications:

Gandara et al., 2017, A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer., J Thorac Oncol

Sun et al., 2014, Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3., Cell Rep

Jing et al., 2012, Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212., Mol. Cancer Ther.

ATEZOLIZUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Atezolizumab + Cobimetinib

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:

Kim et al., 2017, Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review., Oncotarget
IPATASERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
VEMURAFENIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type resistant

Publications:

Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.

CAPIVASERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type stomach cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Li et al., 2013, The AKT inhibitor AZD5363 is selectively active in PI3KCA mutant gastric cancer, and sensitizes a patient-derived gastric cancer xenograft model with PTEN loss to Taxotere., J Transl Med

Yoon et al., 2009, Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells., Mol. Cancer Ther.

LY-3009120 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell

LAPATINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trastuzumab;Lapatinib

Drug family ERBB2 mAb inhibitor;ERBB2 inhibitor

Alteration KRAS:.

Publications:

Sartore-Bianchi et al., 2016, Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial., Lancet Oncol.

DEL-22379 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

Evidence Type Actionable

Approval Status Preclinical

Publications:

Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
AZD-4785 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung cancer

Approval Status Preclinical - Pdx

Indication/Tumor Type non-small cell lung carcinoma

Publications:

Ross et al., 2017, Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS., Sci Transl Med
VOXTALISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Yu et al., 2014, Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathway., Mol. Cancer Ther.
CHEMBL589258 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Mallon et al., 2010, Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor., Mol. Cancer Ther.

ERLOTINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + Alpelisib + Erlotinib + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Brugger et al., 2011, Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer., J. Clin. Oncol.

Ludovini V et al., 2011, Phosphoinositide-3-kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer., J Thorac Oncol

Marchetti et al., 2009, Clinical implications of KRAS mutations in lung cancer patients treated with tyrosine kinase inhibitors: an important role for mutations in minor clones., Neoplasia

INFIGRATINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature

CISPLATIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy MK-1775 + Cisplatin

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Publications:

Chung et al., 2014, A 3'-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma., Ann. Oncol.

Kang et al., 2016, ER2, a novel human anti-EGFR monoclonal antibody inhibit tumor activity in non-small cell lung cancer models., Lung Cancer

Richer et al., 2017, WEE1 Kinase Inhibitor AZD1775 Has Preclinical Efficacy in LKB1-Deficient Non-Small Cell Lung Cancer., Cancer Res.

SARACATINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type intrahepatic cholangiocarcinoma

Response Type sensitive

Approval Status Preclinical

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Saha et al., 2016, Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma., Cancer Discov

PEMETREXED KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pemetrexed + GSK1120212

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Publications:

Gandara et al., 2017, A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer., J Thorac Oncol

DINACICLIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dinaciclib + MK2206

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Danilov et al., 2016, Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2., Mol. Cancer Ther.

Hu et al., 2015, Combined Inhibition of Cyclin-Dependent Kinases (Dinaciclib) and AKT (MK-2206) Blocks Pancreatic Tumor Growth and Metastases in Patient-Derived Xenograft Models., Mol. Cancer Ther.

IRINOTECAN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Irinotecan + Selumetinib

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:

De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.

Ahmed et al., 2013, Epigenetic and genetic features of 24 colon cancer cell lines., Oncogenesis

Smakman et al., 2006, KRAS(D13) Promotes apoptosis of human colorectal tumor cells by ReovirusT3D and oxaliplatin but not by tumor necrosis factor-related apoptosis-inducing ligand., Cancer Res.

OSIMERTINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Indication/Tumor Type non-small cell lung carcinoma

Publications:

Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.

Ortiz-Cuaran et al., 2016, Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors., Clin. Cancer Res.

BORTEZOMIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

Publications:

Kumar et al., 2012, The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer., Cell

AFATINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Afatinib + Cetuximab

Indication/Tumor Type lung adenocarcinoma

Response Type resistant

Publications:

Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.

Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature

Pirazzoli et al., 2016, Afatinib plus Cetuximab Delays Resistance Compared to Single-Agent Erlotinib or Afatinib in Mouse Models of TKI-Naïve EGFR L858R-Induced Lung Adenocarcinoma., Clin. Cancer Res.

OLAPARIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

Publications:

Schmitt et al., 2017, ATM Deficiency Is Associated with Sensitivity to PARP1- and ATR Inhibitors in Lung Adenocarcinoma., Cancer Res.

ABEMACICLIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Evidence Type Actionable

Approval Status Phase I

Publications:

Patnaik et al., 2016, Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors., Cancer Discov

Glover et al., 1992, Gastroenteritis outbreak at an industrial camp--British Columbia., Can. Commun. Dis. Rep.

Sherr et al., 2016, Targeting CDK4 and CDK6: From Discovery to Therapy., Cancer Discov

SUNITINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Phase I

Response Type predicted – sensitive

combination therapy Ixabepilone + Sunitinib

Publications:

Montero et al., 2016, A Phase I Clinical, Pharmacokinetic, and Pharmacodynamic Study of Weekly or Every Three Week Ixabepilone and Daily Sunitinib in Patients with Advanced Solid Tumors., Clin. Cancer Res.

Modest et al., 2013, KRAS allel-specific activity of sunitinib in an isogenic disease model of colorectal cancer., J. Cancer Res. Clin. Oncol.

PONATINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ponatinib + Trametinib

Indication/Tumor Type pancreatic cancer

Response Type sensitive

Publications:

Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature

APITOLISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Soares et al., 2015, Dual PI3K/mTOR Inhibitors Induce Rapid Overactivation of the MEK/ERK Pathway in Human Pancreatic Cancer Cells through Suppression of mTORC2., Mol. Cancer Ther.

Wallin et al., 2011, GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway., Mol. Cancer Ther.

COPANLISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Copanlisib + Refametinib

Indication/Tumor Type biliary tract cancer

Response Type sensitive

Publications:

Liu et al., 2013, BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models., Mol. Cancer Ther.

ALPELISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + Alpelisib + CGM097 + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.

Fernandes MS et al., 2016 Oct 18, Specific inhibition of p110α subunit of PI3K: putative therapeutic strategy for KRAS mutant colorectal cancers., Oncotarget

Fritsch et al., 2014, Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials., Mol. Cancer Ther.

VENETOCLAX KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Venetoclax + VX-11e

Indication/Tumor Type colorectal cancer

Response Type no benefit

Publications:

Anderson et al., 2016, PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation., Sci Transl Med

RAMUCIRUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ramucirumab + FOLFIRI

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Tabernero et al., 2015, Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study., Lancet Oncol.

BINIMETINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type decreased response

Approval Status Preclinical - Cell culture

Publications:

Lee et al., 2016, Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models., Oncotarget

Dhawan et al., 2016, Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling., Nature

Hamidi et al., 2014, KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition., Br. J. Cancer

PANOBINOSTAT KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

Indication/Tumor Type pancreatic ductal adenocarcinoma

combination therapy Panobinostat + SCH772984

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Qian et al., 2012, Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling., Clin. Cancer Res.

Scholl et al., 2009, Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells., Cell

TEMSIROLIMUS KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy SCH772984 + Temsirolimus

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Myers et al., 2016, Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology Group study., Gynecol. Oncol.

OXALIPLATIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Oxaliplatin + ABT-737

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Publications:

Lin et al., 2012, KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells., PLoS ONE

Leone et al., 2016, Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study)., Cancer

Peeters et al., 2015, Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer., Clin. Cancer Res.

NECITUMUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Necitumumab + FOLFOX

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:

Elez et al., 2016, Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer., Br. J. Cancer
PHENFORMIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy MLN0128 + Phenformin

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Publications:

Momcilovic et al., 2015, Heightening Energetic Stress Selectively Targets LKB1-Deficient Non-Small Cell Lung Cancers., Cancer Res.
VISTUSERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy SCH772984 + Vistusertib

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

TRASTUZUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Neratinib + Trastuzumab

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Sartore-Bianchi et al., 2016, Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial., Lancet Oncol.

Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov

EVEROLIMUS KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

Publications:

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

Shoji et al., 2012, Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas., PLoS ONE

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

NERATINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Neratinib + Trastuzumab

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov

A-443654 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Gálvez-Peralta et al., 2014, Context-dependent antagonism between Akt inhibitors and topoisomerase poisons., Mol. Pharmacol.

Dumble et al., 2014, Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor., PLoS ONE

RIDAFOROLIMUS KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ridaforolimus + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
SAR-125844 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type resistant

Publications:

Egile et al., 2015, The selective intravenous inhibitor of the MET tyrosine kinase SAR125844 inhibits tumor growth in MET-amplified cancer., Mol. Cancer Ther.

GEMCITABINE KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type biliary tract cancer

combination therapy Panitumumab + Gemcitabine + Oxaliplatin

Approval Status Phase Ib/II

Publications:

Leone et al., 2016, Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study)., Cancer

Van Laethem et al., 2017, Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer., Target Oncol

O'Neil et al., 2015, A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer., Ann. Oncol.

TASELISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type no benefit

Indication/Tumor Type colorectal cancer

Evidence Type Actionable

Publications:

Juric et al., 2017, Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors., Cancer Discov

NAVITOCLAX KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical

Indication/Tumor Type non-small cell lung carcinoma

combination therapy Trametinib + Navitoclax

Publications:

Lin et al., 2015, The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies., Nat. Genet.

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.

AT-13148 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Yap et al., 2012, AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity., Clin. Cancer Res.

AZD-8835 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

Approval Status Preclinical

Publications:

Hudson et al., 2016, Intermittent High-Dose Scheduling of AZD8835, a Novel Selective Inhibitor of PI3Kα and PI3Kδ, Demonstrates Treatment Strategies for PIK3CA-Dependent Breast Cancers., Mol. Cancer Ther.

IXABEPILONE KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ixabepilone + Sunitinib

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:

Montero et al., 2016, A Phase I Clinical, Pharmacokinetic, and Pharmacodynamic Study of Weekly or Every Three Week Ixabepilone and Daily Sunitinib in Patients with Advanced Solid Tumors., Clin. Cancer Res.

RALIMETINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ralimetinib + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

CARBOPLATIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy XL147 + Carboplatin

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Publications:

Wilson et al., 2016, Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma., Clin. Cancer Res.

Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.

Eberhard et al., 2005, Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib., J. Clin. Oncol.

PIMASERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pimasertib + Gemcitabine

Indication/Tumor Type pancreatic cancer

Response Type sensitive

Publications:

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

Vena et al., 2015, The MEK1/2 Inhibitor Pimasertib Enhances Gemcitabine Efficacy in Pancreatic Cancer Models by Altering Ribonucleotide Reductase Subunit-1 (RRM1)., Clin. Cancer Res.

CI-1040 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Nakayama et al., 2008, KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer., Br. J. Cancer

Yeh et al., 2009, KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer., Mol. Cancer Ther.

DACTOLISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Migliardi et al., 2012, Inhibition of MEK and PI3K/mTOR suppresses tumor growth but does not cause tumor regression in patient-derived xenografts of RAS-mutant colorectal carcinomas., Clin. Cancer Res.

Engelman et al., 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers., Nat. Med.

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

PACLITAXEL KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type resistant

combination therapy Carboplatin + Erlotinib + Paclitaxel

Indication/Tumor Type non-small cell lung carcinoma

Publications:

Wilson et al., 2016, Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma., Clin. Cancer Res.

Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.

Eberhard et al., 2005, Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib., J. Clin. Oncol.

SALIRASIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type no benefit

Approval Status Phase II

Publications:

Riely et al., 2011, A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS mutations., J Thorac Oncol

Laheru D et al., 2012, Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic Acid (FTS, Salirasib) in pancreatic cancer., Invest New Drugs

AZD-8186 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy AZD8186 + BVD-523

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

PF-04691502 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Yuan et al., 2011, PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity., Mol. Cancer Ther.

CC-223 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Dumble et al., 2014, Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor., PLoS ONE

Mortensen et al., 2015, CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization., Mol. Cancer Ther.

PAZOPANIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid cancer

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Ball et al., 2015, Trametinib with and without pazopanib has potent preclinical activity in thyroid cancer., Oncol. Rep.

RIGOSERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Athuluri-Divakar et al., 2016, A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling., Cell

O'Neil et al., 2015, A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer., Ann. Oncol.

AZD-8055 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

Indication/Tumor Type pancreatic ductal adenocarcinoma

combination therapy AZD8055 + SCH772984

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Holt et al., 2012, Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055)., Cancer Res.

Weisberg et al., 2015, Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies., Leukemia

PICTILISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type myelodysplastic/myeloproliferative neoplasm

Response Type sensitive

Approval Status Preclinical

Publications:

Mahoney et al., 2009, LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition., Br. J. Cancer

Qian et al., 2012, Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling., Clin. Cancer Res.

Hoeflich et al., 2012, Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition., Cancer Res.

MIDOSTAURIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Midostaurin + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

RILOTUMUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Rilotumumab + Panitumumab

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Van Cutsem et al., 2014, Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer., Clin. Cancer Res.

DASATINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dasatinib + Demcizumab

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Publications:

Dunn et al., 2011, Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab., Oncogene

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

CABOZANTINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Phase III

Publications:

Sherman et al., 2016, Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer., Cancer

OSI-027 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy OSI-027 + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Bhagwat et al., 2011, Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin., Mol. Cancer Ther.

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

DABRAFENIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Dabrafenib + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.
DEMCIZUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dasatinib + Demcizumab

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Publications:

Ambrogio et al., 2016, Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma., Nat. Med.

PEMBROLIZUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Approval Status Phase I

Publications:

Dong et al., 2017, Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma., Clin. Cancer Res.

Chen et al., 2017, KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung adenocarcinoma., Cancer Immunol. Immunother.

PF-00477736 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy PF3644022 + PF-477736

Indication/Tumor Type urinary bladder cancer

Response Type predicted – sensitive

Publications:

Dietlein et al., 2015, A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer., Cell
VOLASERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Approval Status Preclinical

Publications:

Ferrarotto et al., 2016, Epithelial-Mesenchymal Transition Predicts Polo-Like Kinase 1 Inhibitor-Mediated Apoptosis in Non-Small Cell Lung Cancer., Clin. Cancer Res.
DS-7423 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type ovarian clear cell adenocarcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Kashiyama et al., 2014, Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423., PLoS ONE
RG-7420 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Hatzivassiliou et al., 2013, Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers., Nature

BEVACIZUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Bevacizumab + Sorafenib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Petrelli et al., 2013, KRAS as prognostic biomarker in metastatic colorectal cancer patients treated with bevacizumab: a pooled analysis of 12 published trials., Med. Oncol.

Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.

Venook et al., 2017, Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial., JAMA

SIROLIMUS KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type conflicting

Approval Status Preclinical

Publications:

Yamaguchi et al., 2016, A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers., Oncotarget

Palm et al., 2015, The Utilization of Extracellular Proteins as Nutrients Is Suppressed by mTORC1., Cell

TAZEMETOSTAT KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Selumetinib + Tazemetostat

Indication/Tumor Type lung adenocarcinoma

Response Type no benefit

Publications:

Riquelme et al., 2016, Modulation of EZH2 Expression by MEK-ERK or PI3K-AKT Signaling in Lung Cancer Is Dictated by Different KRAS Oncogene Mutations., Cancer Res.
ERDAFITINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung cancer

Response Type resistant

Approval Status Preclinical - Cell culture

Publications:

Perera et al., 2017, Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor., Mol. Cancer Ther.

REFAMETINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Copanlisib + Refametinib

Indication/Tumor Type biliary tract cancer

Response Type sensitive

Publications:

Gannon et al., 2016, Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy., Mol. Cancer Res.

Van Laethem et al., 2017, Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer., Target Oncol

Lim et al., 2014, A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma., Clin. Cancer Res.

SONOLISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Approval Status Preclinical

Publications:

Yang et al., 2008, Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer., PLoS ONE

PILARALISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy XL147 + Carboplatin

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Publications:

Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.

Foster et al., 2015, The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models., Mol. Cancer Ther.

SAPANISERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Indication/Tumor Type lung cancer

Response Type sensitive

Publications:

Momcilovic et al., 2015, Heightening Energetic Stress Selectively Targets LKB1-Deficient Non-Small Cell Lung Cancers., Cancer Res.

García-García et al., 2015, MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer., Clin. Cancer Res.

PALBOCICLIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Palbociclib + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Ziemke et al., 2016, Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy That Cotargets MEK and CDK4/6., Clin. Cancer Res.

Lee et al., 2016, Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models., Oncotarget

Glover et al., 1992, Gastroenteritis outbreak at an industrial camp--British Columbia., Can. Commun. Dis. Rep.

METFORMIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type endometrial cancer

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Ma et al., 2013, K‑ras gene mutation as a predictor of cancer cell responsiveness to metformin., Mol Med Rep

Iglesias et al., 2013, Another surprise from Metformin: novel mechanism of action via K-Ras influences endometrial cancer response to therapy., Mol. Cancer Ther.

Xie J et al., 2020, Metformin selectively inhibits metastatic colorectal cancer with the <i>KRAS</i> mutation by intracellular accumulation through silencing MATE1., Proc Natl Acad Sci U S A

NILOTINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Nilotinib + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

CAMPTOTHECIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Gedatolisib + Camptothecin

Indication/Tumor Type colon cancer

Response Type sensitive

Publications:

Ahmed et al., 2013, Epigenetic and genetic features of 24 colon cancer cell lines., Oncogenesis

Song et al., 2015, Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer., Clin. Cancer Res.

DOCETAXEL KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Selumetinib + Docetaxel

Indication/Tumor Type non-small cell lung carcinoma

Response Type no benefit

Publications:

Jänne et al., 2015, Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer., Br. J. Cancer

Gandara et al., 2017, A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer., J Thorac Oncol

Jänne et al., 2013, Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study., Lancet Oncol.

RO-4987655 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type no benefit

Approval Status Phase I

Publications:

Nakanishi et al., 2015, ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor., Mol. Cancer Ther.

Zimmer et al., 2014, Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations., Clin. Cancer Res.

ENCORAFENIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Encorafenib

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.

Ahronian et al., 2015, Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations., Cancer Discov

DANUSERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Danusertib + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
LINSITINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Linsitinib + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
CHEMBL217354 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + TW-37

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Publications:

Lin et al., 2015, The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies., Nat. Genet.
ABT 737 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Oxaliplatin + ABT-737

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Publications:

Raats et al., 2011, Synergistic killing of colorectal cancer cells by oxaliplatin and ABT-737., Cell Oncol (Dordr)

FLUOROURACIL KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Panitumumab + Oxaliplatin + Fluorouracil + Irinotecan

Indication/Tumor Type colorectal cancer

Response Type no benefit

Publications:

Peeters et al., 2015, Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer., Clin. Cancer Res.

Douillard et al., 2010, Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study., J. Clin. Oncol.

ULIXERTINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy AZD8186 + BVD-523

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
DOXIL KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Bevacizumab + Temsirolimus + Doxil

Indication/Tumor Type ovarian carcinoma

Response Type sensitive

Publications:

Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.
DECITABINE KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Decitabine;BCL2 inhibitor

Drug family Chemotherapy;BCL2 inhibitor

Alteration KRAS:.

Publications:

Stewart et al., 2015, KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine., Cancer Res.

PD-0325901 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy MLN0128 + PD-0325901

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Mallon et al., 2011, Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor., Clin. Cancer Res.

Janakiraman et al., 2010, Genomic and biological characterization of exon 4 KRAS mutations in human cancer., Cancer Res.

Gannon et al., 2016, Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy., Mol. Cancer Res.

BMS-754807 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BMS-754807 + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
BERZOSERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Approval Status Preclinical

Publications:

Schmitt et al., 2017, ATM Deficiency Is Associated with Sensitivity to PARP1- and ATR Inhibitors in Lung Adenocarcinoma., Cancer Res.
FASUDIL KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy bortezomib + fasudil

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Publications:

Kumar et al., 2012, The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer., Cell

DEGUELIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type stomach cancer

Response Type predicted – sensitive

Approval Status Preclinical

Publications:

Dumble et al., 2014, Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor., PLoS ONE

Lee et al., 2010, Deguelin promotes apoptosis and inhibits angiogenesis of gastric cancer., Oncol. Rep.

POZIOTINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type stomach cancer

Response Type resistant

Approval Status Preclinical

Publications:

Nam et al., 2011, Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer., Cancer Lett.

GEDATOLISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type predicted – sensitive

Approval Status Preclinical - Cell culture

Publications:

Hollestelle et al., 2007, Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines., Mol. Cancer Res.

Ahmed et al., 2013, Epigenetic and genetic features of 24 colon cancer cell lines., Oncogenesis

Acquaviva et al., 2012, Targeting KRAS-mutant non-small cell lung cancer with the Hsp90 inhibitor ganetespib., Mol. Cancer Ther.

ADAVOSERTIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy MK-1775 + Cisplatin

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Publications:

Leijen et al., 2016, Phase II Study of WEE1 Inhibitor AZD1775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line Therapy Within 3 Months., J. Clin. Oncol.

Weisberg et al., 2015, Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies., Leukemia

Richer et al., 2017, WEE1 Kinase Inhibitor AZD1775 Has Preclinical Efficacy in LKB1-Deficient Non-Small Cell Lung Cancer., Cancer Res.

FIMEPINOSTAT KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type multiple myeloma

Response Type sensitive

Approval Status Preclinical

Publications:

Mahoney et al., 2009, LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition., Br. J. Cancer

Janakiraman et al., 2010, Genomic and biological characterization of exon 4 KRAS mutations in human cancer., Cancer Res.

Qian et al., 2012, Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling., Clin. Cancer Res.

CRIZOTINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type stomach cancer

Response Type resistant

Approval Status Preclinical

Publications:

Palma et al., 2014, Durable Response to Crizotinib in a MET-Amplified, KRAS-Mutated Carcinoma of Unknown Primary., Case Rep Oncol

Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature

Kwak et al., 2015, Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer., Cancer Discov

TAK-733 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type cholangiocarcinoma

Response Type sensitive

Approval Status Preclinical - Pdx

Publications:

Lieu et al., 2015, Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts., Oncotarget

PA-799 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type endometrial cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Park et al., 2012, NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations., Int. J. Oncol.

Tanaka et al., 2011, The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations., Clin. Cancer Res.

ROMIDEPSIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

Publications:
CAPECITABINE KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Bevacizumab + Capecitabine

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:
LIFIRAFENIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Approval Status Phase I

Publications:
PANULISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:
SERABELISIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type no benefit

Approval Status Preclinical

Publications:
IMATINIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family BCR-ABL inhibitor 1st gen&KIT inhibitor

Alteration KRAS:G12.

Publications:
XMT-1536 KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Approval Status Preclinical - Pdx

Publications:
NIVOLUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kim et al., 2017, Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review., Oncotarget

CETUXIMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status late trials

Pathway activation

Variant Effect gain-of-function

Publications:

De Roock et al., 2010, Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab., JAMA

Janssen et al., 1987, RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes., Proc. Natl. Acad. Sci. U.S.A.

Lee et al., 2011, Effect of simvastatin on cetuximab resistance in human colorectal cancer with KRAS mutations., J. Natl. Cancer Inst.

PANITUMUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Variant Effect gain-of-function

Pathway activation

Clinical Status FDA-rejected

Publications:

De Roock et al., 2010, Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab., JAMA

Janssen et al., 1987, RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes., Proc. Natl. Acad. Sci. U.S.A.

Lee et al., 2011, Effect of simvastatin on cetuximab resistance in human colorectal cancer with KRAS mutations., J. Natl. Cancer Inst.

TEPROTUMUMAB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ebi et al., 2011, Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers., J. Clin. Invest.

LEUCOVORIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Douillard et al., 2010, Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study., J. Clin. Oncol.

FARNESYL DIPHOSPHATE KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
VANDETANIB KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ensembl: ENSG00000133703
- Version: 101_38
Alternate Names:

KRAS Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
CancerCommons: KRAS
- Version: 25-July-2013
Alternate Names:

3485 Entrez Gene ID

Gene Info:

CancerCommons Reported Gene Name KRAS-RAS

Publications:
TdgClinicalTrial: P01116
- Version: January-2014
Alternate Names:

KRAS Gene Symbol

Gene Info:

Target Class Miscellaneous

Target Subclass Miscellaneous

Target Subclass Hras

Publications:
GuideToPharmacology: 3845
- Version: 29-September-2020
Alternate Names:

6407 HUGO Gene ID

6407 HUGO Gene Symbol

KRAS proto-oncogene, GTPase HUGO Gene Name

Gene Info:

GuideToPharmacology Gene Category Name RAS subfamily

GuideToPharmacology Gene Category ID 897

Gene Categories:

ENZYME

Publications:

JAX-CKB: KRAS

Version: 27-September-2017

Alternate Names:

3845 CKB Entrez Id

KRAS CKB Gene Synonym

C-K-RAS CKB Gene Synonym

Gene Info:

Publications:

Park et al., 2012, NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations., Int. J. Oncol.

Hong et al., 2016, Targeting the PI3K signaling pathway in KRAS mutant colon cancer., Cancer Med

Vansteenkiste et al., 2015, Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study., J Thorac Oncol

PharmGKB: KRAS

Version: 18-August-2020

Alternate Names:

PA30196 PharmGKB ID

Gene Info:

Publications:

De Roock et al., 2010, Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab., JAMA

Gajate P et al., 2012, Influence of KRAS p.G13D mutation in patients with metastatic colorectal cancer treated with cetuximab., Clin Colorectal Cancer

Tejpar et al., 2012, Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab., J. Clin. Oncol.

CIViC: KRAS

Version: 14-September-2020

Alternate Names:

3845 Entrez Gene ID

30 CIViC Gene ID

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE, DRUG RESISTANCE

Publications:

Azuara et al., 2016, Nanofluidic Digital PCR and Extended Genotyping of RAS and BRAF for Improved Selection of Metastatic Colorectal Cancer Patients for Anti-EGFR Therapies., Mol. Cancer Ther.

Patricelli et al., 2016, Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State., Cancer Discov

De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.

DrugBank: BE0004071

Version: 5.1.7

Alternate Names:

KRAS DrugBank Gene Name

P01116 UniProt Accession

3845 Entrez Gene Id

Gene Info:

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

Hallin J et al., 2020, The KRAS<sup>G12C</sup> Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients., Cancer Discov

Canon J et al., 2019, The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity., Nature

CGI: KRAS

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Sherr et al., 2016, Targeting CDK4 and CDK6: From Discovery to Therapy., Cancer Discov

Glover et al., 1992, Gastroenteritis outbreak at an industrial camp--British Columbia., Can. Commun. Dis. Rep.

DoCM: KRAS

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Vogelstein et al., 1990, RAS gene mutations in childhood acute myeloid leukemia: a Pediatric Oncology Group study., Genes Chromosomes Cancer

Brose et al., 2002, BRAF and RAS mutations in human lung cancer and melanoma., Cancer Res.

Douillard et al., 2010, Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study., J. Clin. Oncol.

TALC: K-RAS
- Version: 12-May-2016
Alternate Names:

K-RAS Gene Symbol

Gene Info:

Publications:
OncoKB: KRAS
- Version: 23-July-2020
Alternate Names:

RASK2 OncoKB Gene Synonym

3845 OncoKB Entrez Id

KI-RAS OncoKB Gene Synonym

Gene Info:

Publications:
Tempus: KRAS
- Version: 11-November-2018
Alternate Names:

KRAS Gene Symbol

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
TTD: GTPase KRas
- Version: 2020.06.01
Alternate Names:

KRAS TTD Gene Abbreviation

T48598 TTD Target ID

Gene Info:

Publications:
MskImpact: KRAS
- Version: May-2015
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
MyCancerGenomeClinicalTrial: KRAS
- Version: 30-February-2014
Alternate Names:

Gene Info:

Publications:
ClearityFoundationBiomarkers: KRAS
- Version: 26-July-2013
Alternate Names:

Gene Info:

Publications:
FoundationOneGenes: KRAS
- Version: 03-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
CarisMolecularIntelligence: KRAS
- Version: 04-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
Oncomine: KRAS
- Version: v3
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:

combination therapy	Osimertinib + Selumetinib
Indication/Tumor Type	thyroid cancer
combination therapy	Dasatinib + Selumetinib

Drug family	Pan-kinase inhibitor
Alteration	KRAS:.
Indication/Tumor Type	breast cancer

combination therapy	Reolysin + Gemcitabine
Indication/Tumor Type	pancreatic cancer
Response Type	sensitive

Direct Interaction?	False
Endogenous Drug?	False
Specific Action of the Ligand	Inhibition

combination therapy	BKM120 + AG490
Indication/Tumor Type	stomach cancer
Response Type	sensitive

Indication/Tumor Type	lung adenocarcinoma
Response Type	sensitive
Approval Status	Preclinical - Cell line xenograft

combination therapy	Cetuximab + lenalidomide
Indication/Tumor Type	colorectal cancer
Response Type	predicted – sensitive

combination therapy	Atezolizumab + Cobimetinib
Indication/Tumor Type	colorectal cancer
Response Type	predicted – sensitive

combination therapy	DZNep + MK2206
Indication/Tumor Type	pancreatic cancer
Response Type	sensitive

combination therapy	ABT-263 + Alpelisib + CGM097 + Trametinib
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

combination therapy	Gefitinib + Trametinib
Indication/Tumor Type	lung cancer
Response Type	no benefit

combination therapy	Pazopanib + Trametinib
Indication/Tumor Type	thyroid cancer
combination therapy	Dasatinib + Trametinib

Evidence Type	Actionable
Approval Status	Preclinical - Cell culture
Response Type	sensitive

combination therapy	Trastuzumab;Lapatinib
Drug family	ERBB2 mAb inhibitor;ERBB2 inhibitor
Alteration	KRAS:.

Indication/Tumor Type	non-small cell lung carcinoma
Response Type	sensitive
Approval Status	Preclinical - Cell line xenograft

combination therapy	ABT-263 + Alpelisib + Erlotinib + Trametinib
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

combination therapy	MK-1775 + Cisplatin
Indication/Tumor Type	non-small cell lung carcinoma
Response Type	predicted – sensitive

Indication/Tumor Type	intrahepatic cholangiocarcinoma
Response Type	sensitive
Approval Status	Preclinical

combination therapy	Pemetrexed + GSK1120212
Indication/Tumor Type	non-small cell lung carcinoma
Response Type	predicted – sensitive

combination therapy	Dinaciclib + MK2206
Indication/Tumor Type	pancreatic ductal adenocarcinoma
Response Type	sensitive

KRAS Gene Record

KRAS 3845 Clinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: combination therapy Osimertinib + Selumetinib Indication/Tumor Type thyroid cancer combination therapy Dasatinib + Selumetinib

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Drug family Pan-kinase inhibitor Alteration KRAS:. Indication/Tumor Type breast cancer

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: combination therapy Reolysin + Gemcitabine Indication/Tumor Type pancreatic cancer Response Type sensitive

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction? False Endogenous Drug? False Specific Action of the Ligand Inhibition

Publications:

Interaction Types & Directionality: n/a

Interaction Info: combination therapy BKM120 + AG490 Indication/Tumor Type stomach cancer Response Type sensitive

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung adenocarcinoma Response Type sensitive Approval Status Preclinical - Cell line xenograft

Publications: Gerdes et al., 2013, GA201 (RG7160): a novel, humanized, glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab., Clin. Cancer Res.

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Cetuximab + lenalidomide Indication/Tumor Type colorectal cancer Response Type predicted – sensitive

Publications: Bertino et al., 2016, A Phase I Trial to Evaluate Antibody-Dependent Cellular Cytotoxicity of Cetuximab and Lenalidomide in Advanced Colorectal and Head and Neck Cancer., Mol. Cancer Ther.

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Atezolizumab + Cobimetinib Indication/Tumor Type colorectal cancer Response Type predicted – sensitive

Interaction Types & Directionality: n/a

Interaction Info: combination therapy DZNep + MK2206 Indication/Tumor Type pancreatic cancer Response Type sensitive

Interaction Types & Directionality: n/a

Interaction Info: combination therapy ABT-263 + Alpelisib + CGM097 + Trametinib Indication/Tumor Type colorectal cancer Response Type sensitive

Publications: Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Gefitinib + Trametinib Indication/Tumor Type lung cancer Response Type no benefit

Interaction Types & Directionality: n/a

Interaction Info: Alteration KRAS:. Drug family Pan-TK inhibitor;MEK inhibitor combination therapy Sorafenib;MEK inhibitor

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Pazopanib + Trametinib Indication/Tumor Type thyroid cancer combination therapy Dasatinib + Trametinib

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Atezolizumab + Cobimetinib Indication/Tumor Type colorectal cancer Response Type predicted – sensitive

Publications: Kim et al., 2017, Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review., Oncotarget

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell culture Response Type sensitive

Publications: Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell culture Response Type resistant

Publications: Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type stomach cancer Response Type sensitive Approval Status Preclinical

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type colorectal cancer Response Type sensitive Approval Status Preclinical

Publications: Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Trastuzumab;Lapatinib Drug family ERBB2 mAb inhibitor;ERBB2 inhibitor Alteration KRAS:.

Publications: Sartore-Bianchi et al., 2016, Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial., Lancet Oncol.

Interaction Types & Directionality: n/a

Interaction Info: Approval Status Preclinical - Cell culture Evidence Type Actionable Approval Status Preclinical

Publications: Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung cancer Approval Status Preclinical - Pdx Indication/Tumor Type non-small cell lung carcinoma

Publications: Ross et al., 2017, Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS., Sci Transl Med

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type colorectal cancer Response Type sensitive Approval Status Preclinical - Cell culture

Publications: Yu et al., 2014, Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathway., Mol. Cancer Ther.

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type sensitive Approval Status Preclinical - Cell line xenograft

Publications: Mallon et al., 2010, Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor., Mol. Cancer Ther.

Interaction Types & Directionality: n/a

Interaction Info: combination therapy ABT-263 + Alpelisib + Erlotinib + Trametinib Indication/Tumor Type colorectal cancer Response Type sensitive

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell culture Response Type sensitive

Publications: Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature

Interaction Types & Directionality: n/a

Interaction Info: combination therapy MK-1775 + Cisplatin Indication/Tumor Type non-small cell lung carcinoma Response Type predicted – sensitive

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type intrahepatic cholangiocarcinoma Response Type sensitive Approval Status Preclinical

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Pemetrexed + GSK1120212 Indication/Tumor Type non-small cell lung carcinoma Response Type predicted – sensitive

Publications: Gandara et al., 2017, A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer., J Thorac Oncol

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Dinaciclib + MK2206 Indication/Tumor Type pancreatic ductal adenocarcinoma Response Type sensitive

Interaction Types & Directionality: n/a

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Osimertinib + Selumetinib

Indication/Tumor Type thyroid cancer

combination therapy Dasatinib + Selumetinib

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family Pan-kinase inhibitor

Alteration KRAS:.

Indication/Tumor Type breast cancer

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Reolysin + Gemcitabine

Indication/Tumor Type pancreatic cancer

Response Type sensitive

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BKM120 + AG490

Indication/Tumor Type stomach cancer

Response Type sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Gerdes et al., 2013, GA201 (RG7160): a novel, humanized, glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab., Clin. Cancer Res.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + lenalidomide

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:

Bertino et al., 2016, A Phase I Trial to Evaluate Antibody-Dependent Cellular Cytotoxicity of Cetuximab and Lenalidomide in Advanced Colorectal and Head and Neck Cancer., Mol. Cancer Ther.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Atezolizumab + Cobimetinib

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy DZNep + MK2206

Indication/Tumor Type pancreatic cancer

Response Type sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + Alpelisib + CGM097 + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Gefitinib + Trametinib

Indication/Tumor Type lung cancer

Response Type no benefit

Interaction Types & Directionality:

n/a

Interaction Info:

Alteration KRAS:.

Drug family Pan-TK inhibitor;MEK inhibitor

combination therapy Sorafenib;MEK inhibitor

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pazopanib + Trametinib

Indication/Tumor Type thyroid cancer

combination therapy Dasatinib + Trametinib

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Atezolizumab + Cobimetinib

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Publications:

Kim et al., 2017, Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review., Oncotarget

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type resistant

Publications:

Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type stomach cancer

Response Type sensitive

Approval Status Preclinical

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trastuzumab;Lapatinib

Drug family ERBB2 mAb inhibitor;ERBB2 inhibitor

Alteration KRAS:.

Publications:

Sartore-Bianchi et al., 2016, Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial., Lancet Oncol.

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

Evidence Type Actionable

Approval Status Preclinical

Publications:

Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung cancer

Approval Status Preclinical - Pdx

Indication/Tumor Type non-small cell lung carcinoma

Publications:

Ross et al., 2017, Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS., Sci Transl Med

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Yu et al., 2014, Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathway., Mol. Cancer Ther.

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Mallon et al., 2010, Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor., Mol. Cancer Ther.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + Alpelisib + Erlotinib + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy MK-1775 + Cisplatin

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type intrahepatic cholangiocarcinoma

Response Type sensitive

Approval Status Preclinical

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pemetrexed + GSK1120212

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Publications:

Gandara et al., 2017, A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer., J Thorac Oncol

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dinaciclib + MK2206

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Irinotecan + Selumetinib

Indication/Tumor Type colorectal cancer

Response Type predicted – sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Indication/Tumor Type non-small cell lung carcinoma

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

Publications:

Kumar et al., 2012, The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer., Cell

Interaction Types & Directionality:

n/a

combination therapy	Irinotecan + Selumetinib
Indication/Tumor Type	colorectal cancer
Response Type	predicted – sensitive

combination therapy	Afatinib + Cetuximab
Indication/Tumor Type	lung adenocarcinoma
Response Type	resistant

Approval Status	Phase I
Response Type	predicted – sensitive
combination therapy	Ixabepilone + Sunitinib

combination therapy	Ponatinib + Trametinib
Indication/Tumor Type	pancreatic cancer
Response Type	sensitive

Indication/Tumor Type	colon cancer
Response Type	sensitive
Approval Status	Preclinical - Cell line xenograft

combination therapy	Copanlisib + Refametinib
Indication/Tumor Type	biliary tract cancer
Response Type	sensitive

combination therapy	Venetoclax + VX-11e
Indication/Tumor Type	colorectal cancer
Response Type	no benefit

combination therapy	Ramucirumab + FOLFIRI
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

combination therapy	SCH772984 + Temsirolimus
Indication/Tumor Type	pancreatic ductal adenocarcinoma
Response Type	sensitive

combination therapy	Oxaliplatin + ABT-737
Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive