DGIdb - BRAF Gene Record

BRAF 673 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

673
B-RAF PROTO-ONCOGENE, SERINE/THREONINE KINASE
BRAF
B-RAF1
B-raf
BRAF1
NS7
RAFB1
164757
1097
ENSG00000157764
OTTHUMG00000157457
P15056
PA25408
v-raf murine sarcoma viral oncogene homolog B1
B-RAF PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE (EC 2.7.1.37) (P94) (V-RAF MURINE SARCOMA VIRAL ONCOGENE HOMOLOG B1). [SOURCE:UNIPROT/SWISSPROT;ACC:P15056]
p94
Proto-oncogene B-Raf
Serine/threonine-protein kinase B-raf
TTDS00346
B-RAF PROTEIN
BRAF SERINE/THREONINE KINASE
BRAF(V599E)
B-RAF PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE
1943
NP_004324
NM_004333
5
BE0000634
BRAF1_HUMAN
BRAF_HUMAN
RAF
T99089

Gene Info:

Target Class	Enzymes
Target Subclass	EC:2.7.11.1
Has Variant Annotation	false
Is VIP	false
Human Readable Name	DRUGGABLE GENOME
Human Readable Name	SERINE THREONINE KINASE
GuideToPharmacology Gene Category Name	RAF family
GuideToPharmacology Gene Category ID	610
GuideToPharmacology Gene Type	enzyme
Target Subclass	2.7.11.1
Target Main Class	Enzymes
CancerCommons Reported Gene Name	BRAF (V660) E/K
CancerCommons Reported Gene Name	BRAF
CancerCommons Reported Gene Name	Pan-RAF
CancerCommons Reported Gene Name	BRAF V600E
Interpro Short Name	Ser-Thr/Tyr_kinase_cat_dom
Interpro Name	Serine-threonine/tyrosine-protein kinase catalytic domain
Uniprot Evidence	1: Evidence at protein level
Interpro Acc	IPR001245
Uniprot Status	Swiss-Prot
Interpro Type	Domain
Human Readable Name	KINASE
Source Reported Gene Name	BRAF
Gene Biotype	PROTEIN_CODING

(29 More Sources)

Gene Categories: Category Details

KINASE
SERINE THREONINE KINASE
DRUG RESISTANCE
DRUGGABLE GENOME
CLINICALLY ACTIONABLE

Publications:

Mok et al., 2015, Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition., BMC Cancer
Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.
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
Okimoto RA et al., 2016 Nov 22, Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancer., Proc Natl Acad Sci U S A
Basile et al., 2014, Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors., Pigment Cell Melanoma Res
Wang J et al., 2018, A Secondary Mutation in <i>BRAF</i> Confers Resistance to RAF Inhibition in a <i>BRAF</i><sup>V600E</sup>-Mutant Brain Tumor., Cancer Discov
Dienstmann et al., 2015, Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors., Cancer Discov
Nicolaides et al., 2011, Targeted therapy for BRAFV600E malignant astrocytoma., Clin. Cancer Res.
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.
Rad et al., 2013, A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention., Cancer Cell
Maldonado et al., 2003, Determinants of BRAF mutations in primary melanomas., J. Natl. Cancer Inst.
Yang et al., 2012, Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer., Cancer Res.
Villanueva et al., 2010, Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K., Cancer Cell
Tiacci et al., 2011, BRAF mutations in hairy-cell leukemia., N. Engl. J. Med.
Sosman et al., 2012, Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib., N. Engl. J. Med.
Brose et al., 2002, BRAF and RAS mutations in human lung cancer and melanoma., Cancer Res.
Gupta-Abramson et al., 2008, Phase II trial of sorafenib in advanced thyroid cancer., J. Clin. Oncol.
Ho et al., 2013, Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer., N. Engl. J. Med.
Rizzo et al., 2010, Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?, Cancer Treat. Rev.
Lovly et al., 2012, Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials., PLoS ONE
Falchook et al., 2013, BRAF mutant gastrointestinal stromal tumor: first report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance., Oncotarget
Mao et al., 2013, Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents., Clin. Cancer Res.
Chen et al., 2014, BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis., PLoS ONE
Nakayama et al., 2008, KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer., Br. J. Cancer
Huillard et al., 2012, Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy., Proc. Natl. Acad. Sci. U.S.A.
Peeters et al., 2013, Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer., Clin. Cancer Res.
Nagore et al., 2014, Prognostic value of BRAF mutations in localized cutaneous melanoma., J. Am. Acad. Dermatol.
Pratilas et al., 2008, Genetic predictors of MEK dependence in non-small cell lung cancer., Cancer Res.
McArthur et al., 2014, Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study., Lancet Oncol.
Mao et al., 2011, BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis., Mol. Biol. Rep.
De Roock et al., 2009, Clinical biomarkers in oncology: focus on colorectal cancer., Mol Diagn Ther
Haldar et al., 2011, Epidermal growth factor receptor blockers for the treatment of ovarian cancer., Cochrane Database Syst Rev
Penna et al., 2016, Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade., Oncotarget
Corcoran et al., 2012, EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib., Cancer Discov
Xing et al., 2014, BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence., J. Clin. Oncol.
Tejpar et al., 2010, Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery., Oncologist
Faber et al., 2014, mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1., Cancer Discov
Agaimy et al., 2009, V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours., J. Clin. Pathol.
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.
Kloos et al., 2009, Phase II trial of sorafenib in metastatic thyroid cancer., J. Clin. Oncol.
Ponti et al., 2012, Overwhelming response to Dabrafenib in a patient with double BRAF mutation (V600E; V600M) metastatic malignant melanoma., J Hematol Oncol
Paraiso et al., 2012, The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms., Clin. Cancer Res.
Kirkwood et al., 2012, Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma., Clin. Cancer Res.
Cardarella et al., 2013, Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer., Clin. Cancer Res.
Nissan et al., 2014, Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence., Cancer Res.
Flaherty et al., 2012, Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations., N. Engl. J. Med.
Jalili et al., 2012, Dual suppression of the cyclin-dependent kinase inhibitors CDKN2C and CDKN1A in human melanoma., J. Natl. Cancer Inst.
Gandhi et al., 2009, Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines., PLoS ONE
Rudin et al., 2013, Molecular characterization of acquired resistance to the BRAF inhibitor dabrafenib in a patient with BRAF-mutant non-small-cell lung cancer., J Thorac Oncol
Hauschild et al., 2012, Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial., Lancet
Prahallad et al., 2012, Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR., Nature
Boulalas et al., Mutational analysis of the BRAF gene in transitional cell carcinoma of the bladder., Int. J. Biol. Markers
Sarker et al., 2015, First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors., Clin. Cancer Res.
Crescenzi et al., 2014, Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers., Horm. Metab. Res.
Andrulis et al., 2013, Targeting the BRAF V600E mutation in multiple myeloma., Cancer Discov
Rubinstein et al., 2010, Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032., J Transl Med
Kim et al., 2013, Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation., Thyroid
Dienstmann et al., 2011, BRAF as a target for cancer therapy., Anticancer Agents Med Chem
Chapman et al., 2011, Improved survival with vemurafenib in melanoma with BRAF V600E mutation., N. Engl. J. Med.
Tol et al., 2010, Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab., Eur. J. Cancer
Ji et al., 2013, Vemurafenib synergizes with nutlin-3 to deplete survivin and suppresses melanoma viability and tumor growth., Clin. Cancer Res.
Morris et al., 2013, Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors., Cancer Discov
Sen et al., 2012, Kinase-impaired BRAF mutations in lung cancer confer sensitivity to dasatinib., Sci Transl Med
Patel et al., 2013, Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma., Cancer
He et al., 2014, Prognostic value of the BRAF V600E mutation in papillary thyroid carcinoma., Oncol Lett
Menzies et al., 2014, Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma., Clin. Cancer Res.
Lam et al., 2010, Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer., J. Clin. Oncol.
Di Nicolantonio et al., 2008, Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer., J. Clin. Oncol.
Zecchin et al., 2013, BRAF V600E is a determinant of sensitivity to proteasome inhibitors., Mol. Cancer Ther.
Hayes et al., 2012, Phase II efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements., Clin. Cancer Res.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Meckbach et al., 2014, BRAF-V600 mutations have no prognostic impact in stage IV melanoma patients treated with monochemotherapy., PLoS ONE
Ascierto et al., 2013, Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma., J. Clin. Oncol.
De Roock et al., 2011, KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer., Lancet Oncol.
Walczyk et al., 2014, The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?, Clin. Endocrinol. (Oxf)
Howell et al., 2011, Both BRAF V600E mutation and older age (≥ 65 years) are associated with recurrent papillary thyroid cancer., Ann. Surg. Oncol.
Wan et al., 2004, Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF., Cell
Flaherty et al., 2012, Improved survival with MEK inhibition in BRAF-mutated melanoma., N. Engl. J. Med.
Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.
Kurman et al., 2011, Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm., Hum. Pathol.
Falchook et al., 2012, Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial., Lancet Oncol.
Hatzivassiliou et al., 2013, Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers., Nature
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Rowland et al., 2015, Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer., Br. J. Cancer
Flaherty et al., 2010, Inhibition of mutated, activated BRAF in metastatic melanoma., N. Engl. J. Med.
Ohashi et al., 2012, Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1., Proc. Natl. Acad. Sci. U.S.A.
Falchook et al., 2012, Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial., Lancet
Paik et al., 2011, Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations., J. Clin. Oncol.
Naoki et al., 2002, Missense mutations of the BRAF gene in human lung adenocarcinoma., Cancer Res.
Gautschi et al., 2012, A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib., J Thorac Oncol
Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature
Jordan et al., 2012, Vemurafenib for the treatment of melanoma., Expert Opin Pharmacother
Shi H et al., 2014, Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy., Cancer Discov
Hoogstraat et al., 2015, Detailed imaging and genetic analysis reveal a secondary BRAF(L505H) resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib., Pigment Cell Melanoma Res
Wagenaar et al., 2014, Resistance to vemurafenib resulting from a novel mutation in the BRAFV600E kinase domain., Pigment Cell Melanoma Res
Dahlman et al., 2012, BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors., Cancer Discov
Sahadudheen et al., 2016, Long Term Survival and Continued Complete Response of Vemurafenib in a Metastatic Melanoma Patient with BRAF V600K Mutation., Case Rep Oncol Med
Bahadoran et al., 2013, Major clinical response to a BRAF inhibitor in a patient with a BRAF L597R-mutated melanoma., J. Clin. Oncol.
Hutchinson et al., 2013, BRAF fusions define a distinct molecular subset of melanomas with potential sensitivity to MEK inhibition., Clin. Cancer Res.
Ribas A et al., 2014, Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study., Lancet Oncol
Ascierto PA et al., 2016, Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial., Lancet Oncol
Hyman et al., 2015, Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations., N. Engl. J. Med.
Hainsworth JD et al., 2018, Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study., J Clin Oncol
Silkin SV et al., 2016, Complete Clinical Response of BRAF-Mutated Cholangiocarcinoma to Vemurafenib, Panitumumab, and Irinotecan., J Gastrointest Cancer
Hong et al., 2016, Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation., Cancer Discov
Sharman et al., 2014, Vemurafenib response in 2 patients with posttransplant refractory BRAF V600E-mutated multiple myeloma., Clin Lymphoma Myeloma Leuk
Brose et al., 2016, Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial., Lancet Oncol.
Klempner et al., 2016, BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination Therapy., Cancer Discov
Larkin et al., 2014, Combined vemurafenib and cobimetinib in BRAF-mutated melanoma., N. Engl. J. Med.
Ali et al., 2014, Extended Antitumor Response of a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib., Case Rep Oncol
Savarese et al., beta-Adrenergic receptor decrease in diabetic rat hearts., Life Sci.
Whittaker et al., 2013, A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition., Cancer Discov
Dietrich et al., 2012, BRAF inhibition in refractory hairy-cell leukemia., N. Engl. J. Med.
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
Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature
Nazarian et al., 2010, Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation., Nature
Gautschi et al., 2013, Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib., Lung Cancer
Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov
Peters et al., 2013, Dramatic response induced by vemurafenib in a BRAF V600E-mutated lung adenocarcinoma., J. Clin. Oncol.
Tiacci et al., 2015, Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia., N. Engl. J. Med.
Lin et al., 2015, The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies., Nat. Genet.
Joshi et al., 2015, Trametinib with or without vemurafenib in BRAF mutated non-small cell lung cancer., PLoS ONE
Kotschy et al., 2016, The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models., Nature
Yao et al., 2015, BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition., Cancer Cell
Wagle et al., 2011, Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling., J. Clin. Oncol.
Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov
Chen et al., 2016, Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120., Cancer Discov
Peh et al., 2016, The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas., Mol. Cancer Ther.
Shen et al., 2016, Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma., Nat. Med.
Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell
Zick et al., 2017, Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients., Medicine (Baltimore)
Kirouac et al., 2017, Clinical responses to ERK inhibition in BRAF(V600E)-mutant colorectal cancer predicted using a computational model., NPJ Syst Biol Appl
Bonnevaux et al., 2016, Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor., Mol. Cancer Ther.
Choi et al., 2014, Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors., Pigment Cell Melanoma Res
Kordes et al., 2016, Cooperation of BRAF(F595L) and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling., Leukemia
Banerjee et al., 2016, A Rare Finding of a BRAF Mutation in Renal Cell Carcinoma with Response to BRAF-Directed Targeted Therapy., Cureus
Narita et al., 2014, Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model., Mol. Cancer Ther.
Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.
Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol
Feng et al., 2016, A Novel Plant Sesquiterpene Lactone Derivative, DETD-35, Suppresses BRAFV600E Mutant Melanoma Growth and Overcomes Acquired Vemurafenib Resistance in Mice., Mol. Cancer Ther.
Feng et al., 2015, SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas by Disrupting the eIF4F Translation Initiation Complex., Cancer Res.
Montero-Conde et al., 2013, Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas., Cancer Discov
Yaeger et al., 2015, Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients., Clin. Cancer Res.
Kopetz et al., 2015, Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer., J. Clin. Oncol.
Connolly et al., 2014, Anticancer activity of combination targeted therapy using cetuximab plus vemurafenib for refractory BRAF (V600E)-mutant metastatic colorectal carcinoma., Curr Oncol
Budina-Kolomets et al., 2016, HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors., Cancer Res.
Yang W et al., 2015, Design, synthesis and biological evaluation of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine scaffold as DFG-out B-Raf kinase inhibitors., Eur J Med Chem
Yaeger R et al., 2017, Mechanisms of Acquired Resistance to BRAF V600E Inhibition in Colon Cancers Converge on RAF Dimerization and Are Sensitive to Its Inhibition., Cancer Res
Dankner M et al., 2018, Dual MAPK Inhibition Is an Effective Therapeutic Strategy for a Subset of Class II BRAF Mutant Melanomas., Clin Cancer Res
Sinik L et al., 2019, Inhibition of MERTK Promotes Suppression of Tumor Growth in BRAF Mutant and BRAF Wild-Type Melanoma., Mol Cancer Ther
Mologni L et al., 2018, Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells., Neoplasia
Khater F et al., 2019, Recurrent somatic BRAF insertion (p.V504_R506dup): a tumor marker and a potential therapeutic target in pilocytic astrocytoma., Oncogene
Chapman PB et al., 2017, Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study., Ann Oncol
Woo PYM et al., 2019, Regression of <i>BRAF</i> <sup>V600E</sup> mutant adult glioblastoma after primary combined BRAF-MEK inhibitor targeted therapy: a report of two cases., Oncotarget
Allen A et al., 2019, Rare BRAF mutations in pancreatic neuroendocrine tumors may predict response to RAF and MEK inhibition., PLoS One
Kurzrock R et al., 2020, Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study., Ann Oncol
Caeser R et al., 2019, Targeting MEK in vemurafenib-resistant hairy cell leukemia., Leukemia
Eroglu Z et al., 2018, Combined BRAF and HSP90 Inhibition in Patients with Unresectable <i>BRAF</i> <sup>V600E</sup>-Mutant Melanoma., Clin Cancer Res
Gutzmer R et al., 2020, Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAF<sup>V600</sup> mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial., Lancet
Mazieres J et al., 2020, Vemurafenib in non-small-cell lung cancer patients with BRAF<sup>V600</sup> and BRAF<sup>nonV600</sup> mutations., Ann Oncol
Subbiah V et al., 2020, Pan-Cancer Efficacy of Vemurafenib in <i>BRAF</i> <sup>V600</sup>-Mutant Non-Melanoma Cancers., Cancer Discov
Kaley T et al., 2018, BRAF Inhibition in <i>BRAF</i><sup>V600</sup>-Mutant Gliomas: Results From the VE-BASKET Study., J Clin Oncol
Leaver KE et al., 2016, Response of metastatic glioma to vemurafenib., Neurooncol Pract
Ghosh C et al., 2020, A Combinatorial Strategy for Targeting <i>BRAF</i> <sup>V600E</sup>-Mutant Cancers with BRAF<sup>V600E</sup> Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib)., Clin Cancer Res
Emery CM et al., 2017, BRAF-inhibitor Associated MEK Mutations Increase RAF-Dependent and -Independent Enzymatic Activity., Mol Cancer Res
Sullivan RJ et al., 2019, Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients., Nat Med
Ahronian et al., 2015, Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations., Cancer Discov
Corcoran RB et al., 2018, Combined BRAF, EGFR, and MEK Inhibition in Patients with <i>BRAF</i><sup>V600E</sup>-Mutant Colorectal Cancer., Cancer Discov
2016, Triple Therapy Improves Colorectal Cancer Response., Cancer Discov
Gao Y et al., 2019, V211D Mutation in MEK1 Causes Resistance to MEK Inhibitors in Colon Cancer., Cancer Discov
Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med
Su et al., 2012, RAF265 inhibits the growth of advanced human melanoma tumors., Clin. Cancer Res.
Izar B et al., 2017, A first-in-human phase I, multicenter, open-label, dose-escalation study of the oral RAF/VEGFR-2 inhibitor (RAF265) in locally advanced or metastatic melanoma independent from BRAF mutation status., Cancer Med
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
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.
García-Alfonso P et al., 2018, Single-Agent Regorafenib in Metastatic Colorectal Cancer Patients with Any RAS or BRAF Mutation Previously Treated with FOLFOXIRI plus Bevacizumab (PREVIUM Trial)., Oncologist
Whittaker et al., 2015, Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors., Mol. Cancer Ther.
McNew et al., 2016, MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling., Mol. Cancer Res.
Nikolaev et al., 2011, Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma., Nat. Genet.
Beloueche-Babari et al., 2013, Acute tumour response to the MEK1/2 inhibitor selumetinib (AZD6244, ARRY-142886) evaluated by non-invasive diffusion-weighted MRI., Br. J. Cancer
Friedman et al., 2015, Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment., PLoS ONE
Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.
Emery et al., 2009, MEK1 mutations confer resistance to MEK and B-RAF inhibition., Proc. Natl. Acad. Sci. U.S.A.
Olow et al., 2016, BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas., Clin. Cancer Res.
Lehtomaki KI et al., 2019, Clonal Evolution of MEK/MAPK Pathway Activating Mutations in a Metastatic Colorectal Cancer Case., Anticancer Res
Fangusaro J et al., 2019, Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial., Lancet Oncol
Bardelli et al., 2012, The road to resistance: EGFR mutation and cetuximab., Nat. Med.
Bentivegna et al., 2008, Rapid identification of somatic mutations in colorectal and breast cancer tissues using mismatch repair detection (MRD)., Hum. Mutat.
Girotti et al., 2013, Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma., Cancer Discov
Lu et al., 2017, Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer., Cancer Res.
Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature
Drobysheva et al., 2017, Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas., J Natl Compr Canc Netw
Corcoran et al., 2015, Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer., J. Clin. Oncol.
Long et al., 2016, Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib., J. Clin. Oncol.
Kim et al., 2013, Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor., J. Clin. Oncol.
Marconcini et al., 2017, Metastatic BRAF K601E-mutated melanoma reaches complete response to MEK inhibitor trametinib administered for over 36 months., Exp Hematol Oncol
Carlino et al., 2015, Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients., Clin. Cancer Res.
Long et al., 2014, Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma., N. Engl. J. Med.
Long GV et al., 2017 Sep 10, Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma., N Engl J Med
Ziemke et al., 2016, Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy That Cotargets MEK and CDK4/6., Clin. Cancer Res.
Wagle et al., 2014, MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition., Cancer Discov
Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE
Lange et al., 2014, Biological and molecular effects of small molecule kinase inhibitors on low-passage human colorectal cancer cell lines., Biomed Res Int
Waizenegger et al., 2016, A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation., Mol. Cancer Ther.
Agarwal et al., 2016, Response to Targeted Therapy in BRAF Mutant Anaplastic Thyroid Cancer., J Natl Compr Canc Netw
Schreuer et al., 2017, Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF(V600)-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial., Lancet Oncol.
Gibson et al., 2017, Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer., Clin. Cancer Res.
Teh et al., 2016, An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma., Cancer Res.
Isaacson AL et al., 2019, Urothelial carcinoma with an <i>NRF1-BRAF</i> rearrangement and response to targeted therapy., Cold Spring Harb Mol Case Stud
Aguirre AJ et al., 2018, Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine., Cancer Discov
Long GV et al., 2014, Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma., Nat Commun
Ross et al., 2016, The distribution of BRAF gene fusions in solid tumors and response to targeted therapy., Int. J. Cancer
Bowyer et al., 2014, Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma., Melanoma Res.
Jing et al., 2012, Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212., Mol. Cancer Ther.
Subbiah V et al., 2018, Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer., J Clin Oncol
Robert et al., 2015, Improved overall survival in melanoma with combined dabrafenib and trametinib., N. Engl. J. Med.
Planchard et al., 2016, Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial., Lancet Oncol.
Müller-Gärtner et al., 1989, [Long-term results following surgery or radioiodine treatment of solitary autonomous adenoma of the thyroid gland]., Chirurg
Sakaguchi et al., 1976, Microbiological oxidation of synthetic chalcocite and covellite by Thiobacillus ferrooxidans., Appl. Environ. Microbiol.
Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.
Johnson DB et al., 2020, Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131)., Clin Cancer Res
Noeparast A et al., 2016, Non-V600 BRAF mutations recurrently found in lung cancer predict sensitivity to the combination of Trametinib and Dabrafenib., Oncotarget
Planchard et al., 2016, Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial., Lancet Oncol.
Lin VTG et al., 2018, First-Line Treatment of Widely Metastatic <i>BRAF</i>-Mutated Salivary Duct Carcinoma With Combined BRAF and MEK Inhibition., J Natl Compr Canc Netw
Subbiah V et al., 2020, Dabrafenib plus trametinib in patients with BRAF<sup>V600E</sup>-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial., Lancet Oncol
Xue Y et al., 2017, An approach to suppress the evolution of resistance in BRAF<sup>V600E</sup>-mutant cancer., Nat Med
Johnson DB et al., 2018, BRAF internal deletions and resistance to BRAF/MEK inhibitor therapy., Pigment Cell Melanoma Res
Planchard D et al., 2017, Dabrafenib plus trametinib in patients with previously untreated BRAF<sup>V600E</sup>-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial., Lancet Oncol
Schreck KC et al., 2018, Concurrent BRAF/MEK Inhibitors in <i>BRAF</i> V600-Mutant High-Grade Primary Brain Tumors., J Natl Compr Canc Netw
Owen DH et al., 2019, KRAS G12V Mutation in Acquired Resistance to Combined BRAF and MEK Inhibition in Papillary Thyroid Cancer., J Natl Compr Canc Netw
Abravanel DL et al., 2018, An Acquired NRAS Q61K Mutation in BRAF V600E-Mutant Lung Adenocarcinoma Resistant to Dabrafenib Plus Trametinib., J Thorac Oncol
Persky NS et al., 2020, Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases., Nat Struct Mol Biol
Planchard D et al., 2019, Correction to: "Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up"., Ann Oncol
Planchard D et al., 2018, Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up., Ann Oncol
Olbryt M et al., 2020, Genetic Profiling of Advanced Melanoma: Candidate Mutations for Predicting Sensitivity and Resistance to Targeted Therapy., Target Oncol
Lu et al., 2010, Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway., J Surg Oncol
Flaherty, 2006, Chemotherapy and targeted therapy combinations in advanced melanoma., Clin. Cancer Res.
Kim et al., 2007, Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice., Mol. Cancer Ther.
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Haluska et al., 2006, Therapeutic targets in melanoma: map kinase pathway., Curr Oncol Rep
Eisen et al., 2006, Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis., Br. J. Cancer
Smalley et al., 2009, CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations., Oncogene
Nakaoku et al., 2014, Druggable oncogene fusions in invasive mucinous lung adenocarcinoma., Clin. Cancer Res.
Palanisamy et al., 2010, Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma., Nat. Med.
Gong L et al., 2017, PharmGKB summary: sorafenib pathways., Pharmacogenet Genomics
Hirschi et al., 2014, Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells., Mol. Cancer
Al-Marrawi et al., 2013, Off-label use of cetuximab plus sorafenib and panitumumab plus regorafenib to personalize therapy for a patient with V600E BRAF-mutant metastatic colon cancer., Cancer Biol. Ther.
Mangana et al., 2012, Sorafenib in melanoma., Expert Opin Investig Drugs
Casadei Gardini et al., 2016, Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report., BMC Cancer
Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.
Hoeflich et al., 2009, Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression., Cancer Res.
Dummer R et al., 2018, Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial., Lancet Oncol
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
Ascierto et al., 2013, MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study., Lancet Oncol.
Niessner et al., 2016, PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo., Clin. Cancer Res.
Yan J et al., 2018, Analysis of NRAS gain in 657 patients with melanoma and evaluation of its sensitivity to a MEK inhibitor., Eur J Cancer
Kopetz S et al., 2019, Encorafenib, Binimetinib, and Cetuximab in <i>BRAF</i> V600E-Mutated Colorectal Cancer., N Engl J Med
Dummer R et al., 2018, Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial., Lancet Oncol
Burkart J et al., 2018, Targeting <i>BRAF</i> Mutations in High-Grade Neuroendocrine Carcinoma of the Colon., J Natl Compr Canc Netw
Coit DG et al., 2019, Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology., J Natl Compr Canc Netw
Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.
Tang et al., 2015, BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers., Mol. Cancer Ther.
Desai J et al., 2020, Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors., J Clin Oncol
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.
Rosen LS et al., 2016, A first-in-human phase I study to evaluate the MEK1/2 inhibitor, cobimetinib, administered daily in patients with advanced solid tumors., Invest New Drugs
Diamond EL et al., 2019, Efficacy of MEK inhibition in patients with histiocytic neoplasms., Nature
Anderson et al., 2016, PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation., Sci Transl Med
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.
Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.
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
Peng et al., 2016, Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy., Cancer Discov
Zhao J et al., 2019, Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma., Nat Med
Pires da Silva I et al., 2019, Distinct Molecular Profiles and Immunotherapy Treatment Outcomes of V600E and V600K <i>BRAF</i>-Mutant Melanoma., Clin Cancer Res
Garnett et al., 2012, Systematic identification of genomic markers of drug sensitivity in cancer cells., Nature
Casadevall et al., 2016, Dabrafenib in an elderly patient with metastatic melanoma and BRAF V600R mutation: a case report., J Med Case Rep
Loaiza-Bonilla A et al., 2014, Dramatic response to dabrafenib and trametinib combination in a BRAF V600E-mutated cholangiocarcinoma: implementation of a molecular tumour board and next-generation sequencing for personalized medicine., Ecancermedicalscience
Lavingia V et al., 2016, Impressive response to dual <i>BRAF</i> and MEK inhibition in patients with BRAF mutant intrahepatic cholangiocarcinoma-2 case reports and a brief review., J Gastrointest Oncol
Kocsis J et al., 2017, Combined dabrafenib and trametinib treatment in a case of chemotherapy-refractory extrahepatic BRAF V600E mutant cholangiocarcinoma: dramatic clinical and radiological response with a confusing synchronic new liver lesion., J Gastrointest Oncol
Ponti et al., 2013, The somatic affairs of BRAF: tailored therapies for advanced malignant melanoma and orphan non-V600E (V600R-M) mutations., J. Clin. Pathol.
Gibney et al., 2013, Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies., Expert Opin Drug Metab Toxicol
Garner et al., 1975, Effect of pH on substrate and inhibitor kinetic constants of human liver alanine aminopeptidase. Evidence for two ionizable active center groups., Biochemistry
Poole-Wilson et al., 1975, Effect of pH on ionic exchange and function in rat and rabbit myocardium., Am. J. Physiol.
Fioravanti et al., 1976, Pyridine nucleotide transhydrogenases of parasitic helminths., Arch. Biochem. Biophys.
Bland et al., 1976, Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial., Am. J. Obstet. Gynecol.
Wrzeszczynski KO et al., 2019, Identification of targetable BRAF ΔN486_P490 variant by whole-genome sequencing leading to dabrafenib-induced remission of a <i>BRAF</i>-mutant pancreatic adenocarcinoma., Cold Spring Harb Mol Case Stud
Kieran MW et al., 2019, A Phase I and Pharmacokinetic Study of Oral Dabrafenib in Children and Adolescent Patients with Recurrent or Refractory <i>BRAF</i> V600 Mutation-Positive Solid Tumors., Clin Cancer Res
Hargrave DR et al., 2019, Efficacy and Safety of Dabrafenib in Pediatric Patients with <i>BRAF</i> V600 Mutation-Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I/IIa Study., Clin Cancer Res
van Geel et al., 2017, A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer., Cancer Discov
Montagut et al., 2012, Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer., Nat. Med.
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.
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.
Hsu HC et al., 2016, Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients., Oncotarget
Yao YM et al., 2017, Mouse PDX Trial Suggests Synergy of Concurrent Inhibition of RAF and EGFR in Colorectal Cancer with <i>BRAF</i> or <i>KRAS</i> Mutations., Clin Cancer Res
Ascierto PA et al., 2019, Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial., JAMA Oncol
Dietlein et al., 2015, A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer., Cell
Herath et al., 2016, The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis., Mol. Cancer Ther.
Aung et al., 2016, Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer., Cold Spring Harb Mol Case Stud
Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer
Babiker HM et al., 2019, E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E-mutated metastatic malignant melanoma with brain metastases., Invest New Drugs
Tripathy et al., 2017, Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors., Clin. Cancer Res.
Delord JP et al., 2017, Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic <i>BRAF</i>-Mutant Melanoma., Clin Cancer Res
Moschos SJ et al., 2015, Targeted therapies in melanoma., Surg Oncol Clin N Am
Li Z et al., 2016, Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells., Cancer Lett
Koelblinger P et al., 2018, Development of encorafenib for BRAF-mutated advanced melanoma., Curr Opin Oncol
Hong et al., 2015, Phase I Dose-Escalation Study of the Multikinase Inhibitor Lenvatinib in Patients with Advanced Solid Tumors and in an Expanded Cohort of Patients with Melanoma., Clin. Cancer Res.
Frederick et al., 2014, Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics., PLoS ONE
Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol
Lerner et al., 2015, Targeting a Plk1-Controlled Polarity Checkpoint in Therapy-Resistant Glioblastoma-Propagating Cells., Cancer Res.
Tsai et al., 2008, Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity., Proc. Natl. Acad. Sci. U.S.A.
Berman et al., 2000, The Protein Data Bank., Nucleic Acids 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.
Hassan et al., 2014, Catalytic mTOR inhibitors can overcome intrinsic and acquired resistance to allosteric mTOR inhibitors., Oncotarget
Hollestelle et al., 2007, Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines., Mol. Cancer Res.
Mallon et al., 2011, Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor., Clin. Cancer Res.
Ahmed et al., 2013, Epigenetic and genetic features of 24 colon cancer cell lines., Oncogenesis
James et al., 2012, CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity., Mol. Cancer Ther.
Lieu et al., 2015, Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts., Oncotarget
Acquaviva et al., 2014, Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib., Mol. Cancer Ther.
LaBonte et al., 2011, The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models., Cancer Res.
Sullivan RJ et al., 2020, A Phase I Study of LY3009120, a Pan-RAF Inhibitor, in Patients with Advanced or Metastatic Cancer., Mol Cancer Ther
Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov
Vasbinder MM et al., 2013, Discovery and optimization of a novel series of potent mutant B-Raf(V600E) selective kinase inhibitors., J Med Chem
Solit et al., 2006, BRAF mutation predicts sensitivity to MEK inhibition., Nature
Tanaka et al., 2011, The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations., Clin. Cancer Res.
Nakanishi et al., 2015, ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor., Mol. Cancer Ther.
Iverson et al., 2009, RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer., Cancer Res.
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.
Smith et al., 2015, The HSP90 inhibitor ganetespib potentiates the antitumor activity of EGFR tyrosine kinase inhibition in mutant and wild-type non-small cell lung cancer., Target Oncol
Chang MT et al., 2018, Accelerating Discovery of Functional Mutant Alleles in Cancer., Cancer Discov
Sullivan RJ et al., 2018, First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study., Cancer Discov
Germann UA et al., 2017, Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib)., Mol Cancer Ther
Zhao J et al., 2020, Next-generation sequencing based mutation profiling reveals heterogeneity of clinical response and resistance to osimertinib., Lung Cancer
Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect

PLX8394 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

Publications:

Okimoto RA et al., 2016 Nov 22, Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancer., Proc Natl Acad Sci U S A

Basile et al., 2014, Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors., Pigment Cell Melanoma Res

Wang J et al., 2018, A Secondary Mutation in BRAF Confers Resistance to RAF Inhibition in a BRAFV600E-Mutant Brain Tumor., Cancer Discov

RAF-265 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type predicted – sensitive

Response Type resistant

Indication/Tumor Type Advanced Solid Tumor

Publications:

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

Su et al., 2012, RAF265 inhibits the growth of advanced human melanoma tumors., Clin. Cancer Res.

Izar B et al., 2017, A first-in-human phase I, multicenter, open-label, dose-escalation study of the oral RAF/VEGFR-2 inhibitor (RAF265) in locally advanced or metastatic melanoma independent from BRAF mutation status., Cancer Med

REGORAFENIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

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

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.

DASATINIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status preclinical

Variant Effect reduced kinase activity

Pathway activation

Publications:

Tejpar et al., 2010, Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery., Oncologist

Rizzo et al., 2010, Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?, Cancer Treat. Rev.

Bardelli et al., 2012, The road to resistance: EGFR mutation and cetuximab., Nat. Med.

SORAFENIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Nexavar

Novel drug target Established target

Drug family Pan-TK inhibitor

Publications:

Lu et al., 2010, Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway., J Surg Oncol

Flaherty, 2006, Chemotherapy and targeted therapy combinations in advanced melanoma., Clin. Cancer Res.

Kim et al., 2007, Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice., Mol. Cancer Ther.

LIFIRAFENIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Details of the Assay for Interaction Inhibition of wild type BRAF kinase domain (aa416-766)

Publications:

Tang et al., 2015, BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers., Mol. Cancer Ther.

Desai J et al., 2020, Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors., J Clin Oncol

chembl:CHEMBL525191 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:

Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.

SB590885 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a cell-free assay

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

TEMSIROLIMUS BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

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.

ENCORAFENIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Cetuximab + Encorafenib

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Niessner et al., 2016, PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo., Clin. Cancer Res.

van Geel et al., 2017, A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer., Cancer Discov

Tripathy et al., 2017, Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors., Clin. Cancer Res.

PLX-4720 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell line xenograft

Publications:

Whittaker et al., 2015, Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors., Mol. Cancer Ther.

Wagle et al., 2011, Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling., J. Clin. Oncol.

Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov

CEP-32496 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Inhibition of wild type BRAF activity.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

James et al., 2012, CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity., Mol. Cancer Ther.

LY-3009120 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Dahlman et al., 2012, BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors., Cancer Discov

Chen et al., 2016, Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120., Cancer Discov

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

LGX-806 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:
RG-7256 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:
DABRAFENIB MESYLATE BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:
XL-281 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:
ARQ-736 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Publications:
SORAFENIB TOSYLATE BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:
MLN-2480 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction RAF serine/threonine protein kinase inhibitor

Direct Interaction yes

Publications:
PLX-8394 BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:

VEMURAFENIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status late trials

Clinical Status early trials

Clinical Status case report

Publications:

Dienstmann et al., 2015, Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors., Cancer Discov

Nicolaides et al., 2011, Targeted therapy for BRAFV600E malignant astrocytoma., Clin. Cancer Res.

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.

DABRAFENIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Response Type predicted – resistant

Indication/Tumor Type ovarian cancer

combination therapy AMG 232 + Trametinib + Dabrafenib

Publications:

Lu et al., 2017, Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer., Cancer Res.

Corcoran et al., 2015, Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer., J. Clin. Oncol.

Long et al., 2016, Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib., J. Clin. Oncol.

FOSTAMATINIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:

Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect
ZELBORAF BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Publications:
RIPRETINIB BRAF

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:
PEXIDARTINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy PLX3397 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Mok et al., 2015, Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition., BMC Cancer

OMIPALISIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dabrafenib + GSK2126458

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.

PIMASERTIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pimasertib + Sorafenib

Indication/Tumor Type colorectal 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

SELUMETINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family MEK inhibitor

Alteration BRAF__.

Alteration BRAF:V600E

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

Bonnevaux et al., 2016, Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor., Mol. Cancer Ther.

Whittaker et al., 2015, Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors., Mol. Cancer Ther.

DACTOLISIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BEZ235 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.

Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol

MK-2206 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

combination therapy MK2206 + Trametinib

Indication/Tumor Type melanoma

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

PICTILISIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy GDC0879 + GDC-0941

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.

Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov

Hoeflich et al., 2009, Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression., Cancer Res.

BINIMETINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Encorafenib + Binimetinib

combination therapy Encorafenib + Binimetinib + Cetuximab

Evidence Type Actionable

Publications:

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.

Dummer R et al., 2018, Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial., Lancet Oncol

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

CGM-097 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

Indication/Tumor Type colorectal cancer

combination therapy ABT-263 + CGM097 + Dabrafenib + PF-04217903

Publications:

Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.
PAC-1 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

Peh et al., 2016, The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas., Mol. Cancer Ther.

CI-1040 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

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

Emery et al., 2009, MEK1 mutations confer resistance to MEK and B-RAF inhibition., Proc. Natl. Acad. Sci. U.S.A.

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

CEDIRANIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy Cediranib + Selumetinib + PLX4720

Indication/Tumor Type melanoma

Publications:

Friedman et al., 2015, Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment., PLoS ONE

COBIMETINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status FDA approved

Approval Status Phase Ib/II

combination therapy Atezolizumab + Vemurafenib + Cobimetinib

Publications:

Ribas A et al., 2014, Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study., Lancet Oncol

Ascierto PA et al., 2016, Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial., Lancet Oncol

Larkin et al., 2014, Combined vemurafenib and cobimetinib in BRAF-mutated melanoma., N. Engl. J. Med.

VENETOCLAX BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

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

GEFITINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

combination therapy Gefitinib + PLX4720

Evidence Type Actionable

Publications:

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

Girotti et al., 2013, Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma., Cancer Discov

Corcoran et al., 2012, EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib., Cancer Discov

EVEROLIMUS BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Everolimus + Selumetinib

Indication/Tumor Type malignant glioma

Response Type predicted – sensitive

Publications:

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.

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

BEVACIZUMAB BRAF

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.

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

Yang et al., 2012, Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer., Cancer Res.

PEMBROLIZUMAB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type no benefit

Approval Status Preclinical

Publications:

Peng et al., 2016, Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy., Cancer Discov

Zhao J et al., 2019, Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma., Nat Med

Pires da Silva I et al., 2019, Distinct Molecular Profiles and Immunotherapy Treatment Outcomes of V600E and V600K BRAF-Mutant Melanoma., Clin Cancer Res

GSK-2636771 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy GSK2636771 + Pembrolizumab

combination therapy GSK2636771 + unspecified IGF-1R antibody

combination therapy BYL719 + GSK2636771 + LGX818

Publications:

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.

Peng et al., 2016, Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy., Cancer Discov

OBATOCLAX BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

Publications:

Garnett et al., 2012, Systematic identification of genomic markers of drug sensitivity in cancer cells., Nature
UPROSERTIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov
chembl:CHEMBL217354 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Vemurafenib + TW-37

Indication/Tumor Type non-small cell lung carcinoma

Evidence Type Actionable

Publications:

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

NIVOLUMAB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Phase III

Response Type decreased response

Indication/Tumor Type melanoma

Publications:

Zhao J et al., 2019, Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma., Nat Med

Pires da Silva I et al., 2019, Distinct Molecular Profiles and Immunotherapy Treatment Outcomes of V600E and V600K BRAF-Mutant Melanoma., Clin Cancer Res

Ascierto PA et al., 2019, Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial., JAMA Oncol

AFATINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

Publications:

Waizenegger et al., 2016, A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation., Mol. Cancer Ther.

PF-00477736 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

Indication/Tumor Type Advanced Solid Tumor

Indication/Tumor Type colon cancer

Publications:

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

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Girotti et al., 2013, Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma., Cancer Discov

IRINOTECAN BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Irinotecan

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature

Hsu HC et al., 2016, Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients., Oncotarget

Yang et al., 2012, Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer., Cancer Res.

FLUOROURACIL BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

Publications:

Herath et al., 2016, The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis., Mol. Cancer Ther.

Aung et al., 2016, Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer., Cold Spring Harb Mol Case Stud

BUPARLISIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Binimetinib + BKM120

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

Niessner et al., 2016, PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo., Clin. Cancer Res.

E-6201 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer

Narita et al., 2014, Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model., Mol. Cancer Ther.

Babiker HM et al., 2019, E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E-mutated metastatic malignant melanoma with brain metastases., Invest New Drugs

DOXIL BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Clinical Study

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.

LENVATINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Phase I

Response Type sensitive

Publications:

Hong et al., 2015, Phase I Dose-Escalation Study of the Multikinase Inhibitor Lenvatinib in Patients with Advanced Solid Tumors and in an Expanded Cohort of Patients with Melanoma., Clin. Cancer Res.

SAPANISERTIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy MLN0128 + PD-0325901

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

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.

Hassan et al., 2014, Catalytic mTOR inhibitors can overcome intrinsic and acquired resistance to allosteric mTOR inhibitors., Oncotarget

GEDATOLISIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

Publications:

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

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

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

CAPMATINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type collecting duct carcinoma

Response Type sensitive

Approval Status Preclinical - Pdx

Publications:

Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature

ERLOTINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Erlotinib + PLX4720

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

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

Corcoran et al., 2012, EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib., Cancer Discov

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

TAK-733 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Phase I

Publications:

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

Acquaviva et al., 2014, Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib., Mol. Cancer Ther.

Dahlman et al., 2012, BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors., Cancer Discov

PF-04217903 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + CGM097 + Dabrafenib + PF-04217903

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.

LAPATINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy Lapatinib + Panobinostat

Indication/Tumor Type colorectal cancer

Publications:

Montero-Conde et al., 2013, Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas., Cancer Discov

LaBonte et al., 2011, The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models., Cancer Res.

VORINOSTAT BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type sensitive

Publications:

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

OXALIPLATIN BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type sensitive

Publications:

Herath et al., 2016, The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis., Mol. Cancer Ther.

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

LEUCOVORIN BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

Publications:

Aung et al., 2016, Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer., Cold Spring Harb Mol Case Stud

ATEZOLIZUMAB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Atezolizumab + Vemurafenib + Cobimetinib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Gutzmer R et al., 2020, Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial., Lancet

Sullivan RJ et al., 2019, Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients., Nat Med

NERATINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

Publications:

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

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

Publications:

Aung et al., 2016, Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer., Cold Spring Harb Mol Case Stud
AEW-541 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy AZD6482 + NVP-AEW541

Indication/Tumor Type melanoma

Response Type no benefit

Publications:

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.

NAVITOCLAX BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + Alpelisib + Dabrafenib + Erlotinib

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.

Frederick et al., 2014, Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics., PLoS ONE

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

PD-0325901 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type resistant

Approval Status Preclinical

Publications:

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.

Teh et al., 2016, An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma., Cancer Res.

Lerner et al., 2015, Targeting a Plk1-Controlled Polarity Checkpoint in Therapy-Resistant Glioblastoma-Propagating Cells., Cancer Res.

PA-799 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type breast cancer

Response Type decreased response

Approval Status Preclinical - Cell line xenograft

Publications:

Tanaka et al., 2011, The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations., Clin. Cancer Res.
RO-4987655 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

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

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type rectum cancer

Evidence Type Actionable

Approval Status Guideline

Publications:

Hainsworth JD et al., 2018, Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study., J Clin Oncol

ALPELISIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Alpelisib + PLX4720

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

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

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

van Geel et al., 2017, A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer., Cancer Discov

PALBOCICLIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

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

Teh et al., 2016, An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma., Cancer Res.

DEL-22379 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

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

DOXORUBICIN BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy PLX4720 + Doxorubicin

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

IMATINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell line xenograft

combination therapy Imatinib + PLX4720

Evidence Type Actionable

Publications:

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

AZD-6482 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy AZD6482 + NVP-AEW541

Indication/Tumor Type melanoma

Response Type no benefit

Publications:

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.
REFAMETINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Iverson et al., 2009, RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer., Cancer Res.

PANOBINOSTAT BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Lapatinib + Panobinostat

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

LaBonte et al., 2011, The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models., Cancer Res.

TIVOZANIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy PLX4720 + Tivozanib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Friedman et al., 2015, Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment., PLoS ONE
RIBOCICLIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Encorafenib + Ribociclib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Tripathy et al., 2017, Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors., Clin. Cancer Res.
IDELALISIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type no benefit

Approval Status Preclinical

Publications:

Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol

SAR-260301 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy SAR260301 + Selumetinib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Bonnevaux et al., 2016, Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor., Mol. Cancer Ther.

XL-888 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Paraiso et al., 2012, The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms., Clin. Cancer Res.

Eroglu Z et al., 2018, Combined BRAF and HSP90 Inhibition in Patients with Unresectable BRAF V600E-Mutant Melanoma., Clin Cancer Res

PILARALISIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

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.

GANETESPIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type skin melanoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Smith et al., 2015, The HSP90 inhibitor ganetespib potentiates the antitumor activity of EGFR tyrosine kinase inhibition in mutant and wild-type non-small cell lung cancer., Target Oncol

Acquaviva et al., 2014, Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib., Mol. Cancer Ther.

ULIXERTINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

Indication/Tumor Type colorectal cancer

Approval Status Preclinical - Cell line xenograft

Publications:

Chang MT et al., 2018, Accelerating Discovery of Functional Mutant Alleles in Cancer., Cancer Discov

Sullivan RJ et al., 2018, First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study., Cancer Discov

Germann UA et al., 2017, Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib)., Mol Cancer Ther

PONATINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

combination therapy Ponatinib + Vemurafenib

Evidence Type Actionable

Publications:

Ghosh C et al., 2020, A Combinatorial Strategy for Targeting BRAF V600E-Mutant Cancers with BRAFV600E Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib)., Clin Cancer Res

OSIMERTINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Case Reports/Case Series

Response Type predicted - resistant

Publications:

Zhao J et al., 2020, Next-generation sequencing based mutation profiling reveals heterogeneity of clinical response and resistance to osimertinib., Lung Cancer
MIRANSERTIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Pdx

Response Type sensitive

Publications:

Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE
SAPITINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Patient cell culture

Response Type predicted - sensitive

Publications:

Lehtomaki KI et al., 2019, Clonal Evolution of MEK/MAPK Pathway Activating Mutations in a Metastatic Colorectal Cancer Case., Anticancer Res
VORUCICLIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Vemurafenib + Voruciclib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:
CRIZOTINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Crizotinib;Vemurafenib

Drug family ALK inhibitor;BRAF inhibitor

Alteration MET:amp;BRAF:V600E

Publications:

PANITUMUMAB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Alteration MET:amp;BRAF:V600E

Drug family BRAF inhibitor;EGFR mAb inhibitor

combination therapy Vemurafenib;Panitumumab

Publications:

Peeters et al., 2013, Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer., Clin. Cancer Res.

De Roock et al., 2011, KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer., Lancet Oncol.

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.

TRAMETINIB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Lu et al., 2017, Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer., Cancer Res.

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

Drobysheva et al., 2017, Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas., J Natl Compr Canc Netw

CAPECITABINE BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Yang et al., 2012, Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer., Cancer Res.

CETUXIMAB BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + PLX4720

combination therapy Vemurafenib + Cetuximab

combination therapy Cetuximab + Dabrafenib + SCH772984

Publications:

Hyman et al., 2015, Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations., N. Engl. J. Med.

van Geel et al., 2017, A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer., Cancer Discov

Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature

chembl:CHEMBL2144069 BRAF

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Vasbinder MM et al., 2013, Discovery and optimization of a novel series of potent mutant B-Raf(V600E) selective kinase inhibitors., J Med Chem

Ensembl: ENSG00000157764
- Version: 101_38
Alternate Names:

BRAF Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
TdgClinicalTrial: P15056
- Version: January-2014
Alternate Names:

BRAF Gene Symbol

Gene Info:

Target Class Enzymes

Target Subclass EC:2.7.11.1

Publications:

RussLampel: ENSG00000157764

Version: 26-July-2011

Alternate Names:

ENSG00000157764 Ensembl Gene Id

BRAF Display Id

B-RAF PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE (EC 2.7.1.37) (P94) (V-RAF MURINE SARCOMA VIRAL ONCOGENE HOMOLOG B1). [SOURCE:UNIPROT/SWISSPROT;ACC:P15056] Description

Gene Info:

Human Readable Name DRUGGABLE GENOME

Gene Categories:

DRUGGABLE GENOME

Publications:

TEND: P15056
- Version: 01-August-2011
Alternate Names:

BRAF1_HUMAN Uniprot Id

ENSG00000157764 Ensembl Gene Id

P15056 Uniprot Accession

Gene Info:

Target Subclass 2.7.11.1

Target Main Class Enzymes

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

673 Entrez Gene ID

Gene Info:

CancerCommons Reported Gene Name BRAF (V660) E/K

CancerCommons Reported Gene Name BRAF

CancerCommons Reported Gene Name Pan-RAF

Publications:
HopkinsGroom: P15056
- Version: 11-September-2012
Alternate Names:

SERINE/THREONINE-PROTEIN KINASE B-RAF Uniprot Protein Name

BRAF_HUMAN Uniprot Id

673 Entrez Gene Id

Gene Info:

Interpro Short Name Ser-Thr/Tyr_kinase_cat_dom

Interpro Name Serine-threonine/tyrosine-protein kinase catalytic domain

Uniprot Evidence 1: Evidence at protein level

Gene Categories:

KINASE, DRUGGABLE GENOME

Publications:
GuideToPharmacologyGenes: 1943
- Version: 4-March-2015
Alternate Names:

B-Raf proto-oncogene, serine/threonine kinase HUGO Gene Name

1097 HUGO Gene ID

BRAF Gene Symbol

Gene Info:

GuideToPharmacology Gene Category Name RAF family

GuideToPharmacology Gene Category ID 610

GuideToPharmacology Gene Type enzyme

Gene Categories:

SERINE THREONINE KINASE, KINASE

Publications:
PharmGKB: BRAF
- Version: 18-August-2020
Alternate Names:

PA25408 PharmGKB ID

Gene Info:

Publications:

Gong L et al., 2017, PharmGKB summary: sorafenib pathways., Pharmacogenet Genomics

JAX-CKB: BRAF

Version: 15-September-2020

Alternate Names:

673 CKB Entrez Id

BRAF CKB Gene Synonym

B-raf CKB Gene Synonym

Gene Info:

Publications:

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

Carlino et al., 2015, Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients., Clin. Cancer Res.

Shao W et al., 2018, Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF., Cancer Res

DrugBank: BE0000634

Version: 5.1.7

Alternate Names:

BRAF DrugBank Gene Name

P15056 UniProt Accession

673 Entrez Gene Id

Gene Info:

Publications:

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Haluska et al., 2006, Therapeutic targets in melanoma: map kinase pathway., Curr Oncol Rep

Flaherty, 2006, Chemotherapy and targeted therapy combinations in advanced melanoma., Clin. Cancer Res.

DoCM: BRAF

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature

Gautschi et al., 2012, A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib., J Thorac Oncol

Naoki et al., 2002, Missense mutations of the BRAF gene in human lung adenocarcinoma., Cancer Res.

DTC: BRAF

Version: 02-September-2020

Alternate Names:

Gene Info:

Publications:

Yang W et al., 2015, Design, synthesis and biological evaluation of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine scaffold as DFG-out B-Raf kinase inhibitors., Eur J Med Chem

Vasbinder MM et al., 2013, Discovery and optimization of a novel series of potent mutant B-Raf(V600E) selective kinase inhibitors., J Med Chem

CGI: BRAF

Version: 14-September-2020

Alternate Names:

Gene Info:

Publications:

Kim et al., 2013, Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor., J. Clin. Oncol.

Falchook et al., 2012, Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial., Lancet Oncol.

Nakaoku et al., 2014, Druggable oncogene fusions in invasive mucinous lung adenocarcinoma., Clin. Cancer Res.

HingoraniCasas: ENSG00000157764
- Version: 31-May-2017
Alternate Names:

ENSG00000157764 Gene Symbol

BRAF Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

Publications:
TALC: BRAF
- Version: 12-May-2016
Alternate Names:

BRAF Gene Symbol

Gene Info:

Publications:
MyCancerGenome: BRAF
- Version: 20-Jun-2017
Alternate Names:

673 Entrez Gene Id

BRAF MyCancerGenome Gene Symbol

BRAF MyCancerGenome Reported Gene Name

Gene Info:

Publications:
ChemblInteractions: BRAF1
- Version: chembl_23
Alternate Names:

RAFB1 GENE_SYMBOL

BRAF GENE_SYMBOL

Serine/threonine-protein kinase B-raf UNIPROT

Gene Info:

Publications:
GuideToPharmacologyInteractions: ENSG00000157764
- Version: 20-July-2020
Alternate Names:

B-Raf proto-oncogene, serine/threonine kinase GuideToPharmacology Name

P15056 UniProtKB ID

Gene Info:

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

673 OncoKB Entrez Id

NS7 OncoKB Gene Synonym

B-raf OncoKB Gene Synonym

Gene Info:

Publications:
TTD: Serine/threonine-protein kinase B-raf
- Version: 2020.06.01
Alternate Names:

BRAF TTD Gene Abbreviation

T99089 TTD Target ID

Gene Info:

Publications:
Pharos: BRAF
- Version: 03-September-2020
Alternate Names:

Serine/threonine-protein kinase B-raf Gene Name

P15056 UniProt ID

Gene Info:

Gene Categories:

KINASE

Publications:
GO: BRAF
- Version: 05-September-2020
Alternate Names:

BRAF1 GO Gene Synonym

RAFB1 GO Gene Synonym

Gene Info:

Gene Categories:

SERINE THREONINE KINASE

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

BRAF Gene Symbol

Gene Info:

Publications:
dGene: BRAF
- Version: 27-Jun-2013
Alternate Names:

673 Gene ID

B-RAF1 dGene Synonym

BRAF1 dGene Synonym

Gene Info:

Gene Categories:

SERINE THREONINE KINASE, KINASE

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

Gene Info:

Publications:
ClearityFoundationClinicalTrial: BRAF
- Version: 15-June-2013
Alternate Names:

Gene Info:

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

Gene Info:

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
FDA: BRAF
- Version: 04-September-2020
Alternate Names:

Gene Info:

Publications:
COSMIC: BRAF
- Version: 4-Sep-2020
Alternate Names:

Gene Info:

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:

Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive
Approval Status	Preclinical

Response Type	predicted – sensitive
Response Type	resistant
Indication/Tumor Type	Advanced Solid Tumor

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

Clinical Status	preclinical
Variant Effect	reduced kinase activity
Pathway	activation

Trial Name	Nexavar
Novel drug target	Established target
Drug family	Pan-TK inhibitor

Direct Interaction	yes
Mechanism of Interaction	Serine/threonine-protein kinase B-raf inhibitor
Details of the Assay for Interaction	Inhibition of wild type BRAF kinase domain (aa416-766)

Details of the Assay for Interaction	In a cell-free assay
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

combination therapy	Bevacizumab + Temsirolimus + Doxil
Indication/Tumor Type	ovarian carcinoma
Response Type	sensitive

combination therapy	Cetuximab + Encorafenib
Indication/Tumor Type	colorectal cancer
Response Type	resistant

Indication/Tumor Type	melanoma
Response Type	resistant
Approval Status	Preclinical - Cell line xenograft

Details of the Assay for Interaction	Inhibition of wild type BRAF activity.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Mechanism of Interaction	RAF serine/threonine protein kinase inhibitor
Direct Interaction	yes

Clinical Status	late trials
Clinical Status	early trials
Clinical Status	case report

Response Type	predicted – resistant
Indication/Tumor Type	ovarian cancer
combination therapy	AMG 232 + Trametinib + Dabrafenib

combination therapy	PLX3397 + Vemurafenib
Indication/Tumor Type	melanoma
Response Type	sensitive

combination therapy	Dabrafenib + GSK2126458
Indication/Tumor Type	melanoma
Response Type	sensitive

combination therapy	Pimasertib + Sorafenib
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

Drug family	MEK inhibitor
Alteration	BRAF__.
Alteration	BRAF:V600E

combination therapy	BEZ235 + Vemurafenib
Indication/Tumor Type	melanoma
Response Type	sensitive

Evidence Type	Actionable
combination therapy	MK2206 + Trametinib
Indication/Tumor Type	melanoma

BRAF Gene Record

BRAF 673 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type Advanced Solid Tumor Response Type sensitive Approval Status Preclinical

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Response Type predicted – sensitive Response Type resistant Indication/Tumor Type Advanced Solid Tumor

Interaction Types & Directionality: inhibitor (inhibitory)

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

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Clinical Status preclinical Variant Effect reduced kinase activity Pathway activation

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name Nexavar Novel drug target Established target Drug family Pan-TK inhibitor

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Details of the Assay for Interaction Inhibition of wild type BRAF kinase domain (aa416-766)

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications: Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction In a cell-free assay Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications: Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

Interaction Types & Directionality: inhibitor (inhibitory)

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.

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: combination therapy Cetuximab + Encorafenib Indication/Tumor Type colorectal cancer Response Type resistant

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type melanoma Response Type resistant Approval Status Preclinical - Cell line xenograft

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction Inhibition of wild type BRAF activity. Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications: James et al., 2012, CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity., Mol. Cancer Ther.

Interaction Types & Directionality: inhibitor (inhibitory)

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

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction RAF serine/threonine protein kinase inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Clinical Status late trials Clinical Status early trials Clinical Status case report

Interaction Types & Directionality: inhibitor (inhibitory) antagonist (inhibitory)

Interaction Info: Response Type predicted – resistant Indication/Tumor Type ovarian cancer combination therapy AMG 232 + Trametinib + Dabrafenib

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

Publications: Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Reported Cancer Type Melanoma

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info: combination therapy PLX3397 + Vemurafenib Indication/Tumor Type melanoma Response Type sensitive

Publications: Mok et al., 2015, Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition., BMC Cancer

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Dabrafenib + GSK2126458 Indication/Tumor Type melanoma Response Type sensitive

Publications: Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.

Interaction Types & Directionality: n/a

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type predicted – sensitive

Response Type resistant

Indication/Tumor Type Advanced Solid Tumor

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status preclinical

Variant Effect reduced kinase activity

Pathway activation

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Nexavar

Novel drug target Established target

Drug family Pan-TK inhibitor

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Details of the Assay for Interaction Inhibition of wild type BRAF kinase domain (aa416-766)

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:

Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a cell-free assay

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

Interaction Types & Directionality:

inhibitor (inhibitory)

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.

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Cetuximab + Encorafenib

Indication/Tumor Type colorectal cancer

Response Type resistant

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell line xenograft

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Inhibition of wild type BRAF activity.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

James et al., 2012, CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity., Mol. Cancer Ther.

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction RAF serine/threonine protein kinase inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status late trials

Clinical Status early trials

Clinical Status case report

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Response Type predicted – resistant

Indication/Tumor Type ovarian cancer

combination therapy AMG 232 + Trametinib + Dabrafenib

Interaction Types & Directionality:

inhibitor (inhibitory)

Publications:

Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy PLX3397 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Mok et al., 2015, Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition., BMC Cancer

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dabrafenib + GSK2126458

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pimasertib + Sorafenib

Indication/Tumor Type colorectal 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

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family MEK inhibitor

Alteration BRAF__.

Alteration BRAF:V600E

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BEZ235 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

combination therapy MK2206 + Trametinib

Indication/Tumor Type melanoma

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy GDC0879 + GDC-0941

Indication/Tumor Type melanoma

Response Type sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Encorafenib + Binimetinib

combination therapy Encorafenib + Binimetinib + Cetuximab

Evidence Type Actionable

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Preclinical - Cell culture

Indication/Tumor Type colorectal cancer

combination therapy ABT-263 + CGM097 + Dabrafenib + PF-04217903

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:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

combination therapy	GDC0879 + GDC-0941
Indication/Tumor Type	melanoma
Response Type	sensitive

combination therapy	Encorafenib + Binimetinib
combination therapy	Encorafenib + Binimetinib + Cetuximab
Evidence Type	Actionable

Approval Status	Preclinical - Cell culture
Indication/Tumor Type	colorectal cancer
combination therapy	ABT-263 + CGM097 + Dabrafenib + PF-04217903

Approval Status	FDA approved
Approval Status	Phase Ib/II
combination therapy	Atezolizumab + Vemurafenib + Cobimetinib

combination therapy	Everolimus + Selumetinib
Indication/Tumor Type	malignant glioma
Response Type	predicted – sensitive

combination therapy	GSK2636771 + Pembrolizumab
combination therapy	GSK2636771 + unspecified IGF-1R antibody
combination therapy	BYL719 + GSK2636771 + LGX818

combination therapy	Vemurafenib + TW-37
Indication/Tumor Type	non-small cell lung carcinoma
Evidence Type	Actionable

Approval Status	Phase III
Response Type	decreased response
Indication/Tumor Type	melanoma

combination therapy	Cetuximab + Irinotecan
Indication/Tumor Type	colorectal cancer
Response Type	resistant

combination therapy	Fluorouracil + Leucovorin + Trastuzumab
Indication/Tumor Type	rectum adenocarcinoma
Response Type	no benefit