DGIdb - LAPATINIB Drug Record

LAPATINIB chembl:CHEMBL554 ApprovedAntineoplastic

Alternate Names:

TYVERB
GW-572016X
GSK-572016
LAPATINIB
GW-2016
GW-572016
GW572016
LAP016
N-{3-CHLORO-4-[(3-FLUOROBENZYL)OXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURYL]-4-QUINAZOLINAMINE
GW 572016
FMM
N-{3-CHLORO-4-[(3-FLUOROPHENYL)METHOXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURANYL]-4-QUINAZOLINAMINE
chembl:CHEMBL554
pubchem.compound:208908
chemidplus:231277-92-2
rxcui:480167
drugbank:01259

Drug Info:

FDA Approval	Breast cancer (HER2+)
Drug Class	Kinase Inhibitors
FDA Approval	approved
Drug Class	Small Molecule
Drug Indications	antineoplastic agent
Year of Approval	2007
Drug Class	antineoplastic agents, protein kinase inhibitors
Pharmaceutical Developer	GlaxoSmithKline
Source Reported Drug Name(s)	Lapatinib
Drug Class	EGFR inhibitor

(15 More Sources)

Publications:

Scott et al., 1991, The effects of flosequinan on regional blood flow in normal man., Br J Clin Pharmacol
Lorenzen et al., 2015, Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie., Eur. J. Cancer
Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov
Greulich et al., 2012, Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2., Proc. Natl. Acad. Sci. U.S.A.
Grellety et al., 2016, A clinical case of invasive lobular breast carcinoma with ERBB2 and CDH1 mutations presenting a dramatic response to anti-HER2-directed therapy., Ann. Oncol.
Boulbes et al., 2015, HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer., Mol Oncol
Sartore-Bianchi et al., 2016, Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial., Lancet Oncol.
Manole et al., 2016, JNK Pathway Activation Modulates Acquired Resistance to EGFR/HER2-Targeted Therapies., Cancer Res.
Witkiewicz et al., 2014, CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models., Genes Cancer
Clavarezza et al., 2016, Dual Block with Lapatinib and Trastuzumab Versus Single-Agent Trastuzumab Combined with Chemotherapy as Neoadjuvant Treatment of HER2-Positive Breast Cancer: A Meta-analysis of Randomized Trials., Clin. Cancer Res.
Satoh et al., 2014, Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study., J. Clin. Oncol.
Johnston et al., 2009, Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer., J. Clin. Oncol.
Wisinski et al., 2016, Phase I Study of an AKT Inhibitor (MK-2206) Combined with Lapatinib in Adult Solid Tumors Followed by Dose Expansion in Advanced HER2+ Breast Cancer., Clin. Cancer Res.
Baselga et al., 2016, Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer., Clin. Cancer Res.
Guarneri et al., 2015, Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer., Oncologist
Li et al., 2014, Modulation of ErbB2 blockade in ErbB2-positive cancers: the role of ErbB2 Mutations and PHLDA1., PLoS ONE
Rexer et al., 2013, Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2., Clin. Cancer Res.
de Martino et al., 2014, Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib., Cancer Biol. Ther.
Biswas et al., 2016, Genomic profiling of multiple sequentially acquired tumor metastatic sites from an "exceptional responder" lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response., Cold Spring Harb Mol Case Stud
Zuo et al., 2016, Dual Characteristics of Novel HER2 Kinase Domain Mutations in Response to HER2-Targeted Therapies in Human Breast Cancer., Clin. Cancer Res.
Morrison Joly et al., 2016, Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers., Cancer Res.
Hecht et al., 2016, Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial., J. Clin. Oncol.
Kotschy et al., 2016, The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models., Nature
Leto et al., 2015, Sustained Inhibition of HER3 and EGFR Is Necessary to Induce Regression of HER2-Amplified Gastrointestinal Carcinomas., Clin. Cancer Res.
Bertotti et al., 2011, A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer., Cancer Discov
Wainberg et al., 2010, Lapatinib, a dual EGFR and HER2 kinase inhibitor, selectively inhibits HER2-amplified human gastric cancer cells and is synergistic with trastuzumab in vitro and in vivo., Clin. Cancer Res.
Kwak et al., 2015, Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer., Cancer Discov
Secrier et al., 2016, Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance., Nat. Genet.
Bose et al., 2013, Activating HER2 mutations in HER2 gene amplification negative breast cancer., Cancer Discov
Kancha et al., 2011, Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib., PLoS ONE
Trowe et al., 2008, EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation., Clin. Cancer Res.
Pan et al., 2015, Development and Characterization of Bladder Cancer Patient-Derived Xenografts for Molecularly Guided Targeted Therapy., PLoS ONE
Hanker et al., 2013, Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies., Proc. Natl. Acad. Sci. U.S.A.
Kim et al., 2008, The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines., Cancer Lett.
Cancer Cell Line Encyclopedia Consortium. et al., 2015, Pharmacogenomic agreement between two cancer cell line data sets., Nature
Lyu A et al., 2014, Design and synthesis of Lapatinib derivatives containing a branched side chain as HER1/HER2 targeting antitumor drug candidates., Eur J Med Chem
Sridhar J et al., 2014, Identification of quinones as HER2 inhibitors for the treatment of trastuzumab resistant breast cancer., Bioorg Med Chem Lett
Ali et al., 2014, Response of an ERBB2-mutated inflammatory breast carcinoma to human epidermal growth factor receptor 2-targeted therapy., J. Clin. Oncol.
Lee et al., 2006, Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas., Clin. Cancer Res.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Geyer et al., 2006, Lapatinib plus capecitabine for HER2-positive advanced breast cancer., N. Engl. J. Med.
Xia et al., 2005, Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells., Oncogene
Baselga et al., 2012, Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial., Lancet
Lee et al., 2016, Serum Human Epidermal Growth Factor 2 Extracellular Domain as a Predictive Biomarker for Lapatinib Treatment Efficacy in Patients With Advanced Breast Cancer., J. Clin. Oncol.
Guarneri et al., 2012, Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study., J. Clin. Oncol.
Blackwell et al., 2010, Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer., J. Clin. Oncol.
Xia et al., 2002, Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways., Oncogene
Johnston et al., 2006, Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer., Drugs Today
Zhou et al., 2004, Effects of the EGFR/HER2 kinase inhibitor GW572016 on EGFR- and HER2-overexpressing breast cancer cell line proliferation, radiosensitization, and resistance., Int. J. Radiat. Oncol. Biol. Phys.
Tevaarwerk et al., 2009, Lapatinib: a small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer., Clin Ther
Vazquez-Martin et al., 2011, Lapatinib, a dual HER1/HER2 tyrosine kinase inhibitor, augments basal cleavage of HER2 extracellular domain (ECD) to inhibit HER2-driven cancer cell growth., J. Cell. Physiol.
Wood et al., 2004, A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells., Cancer Res.
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Grana et al., 2003, Epidermal growth factor receptor autocrine signaling in RIE-1 cells transformed by the Ras oncogene enhances radiation resistance., Cancer Res.
Burris, 2004, Dual kinase inhibition in the treatment of breast cancer: initial experience with the EGFR/ErbB-2 inhibitor lapatinib., Oncologist
Xia et al., 2004, Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016., Oncogene
Langer, 2004, Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC., Int. J. Radiat. Oncol. Biol. Phys.
Medina et al., 2008, Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases., Clin Ther
Bachelot T et al., 2013, Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study., Lancet Oncol
Lin NU et al., 2009, Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer., Clin Cancer Res
Leary et al., 2015, Antiproliferative Effect of Lapatinib in HER2-Positive and HER2-Negative/HER3-High Breast Cancer: Results of the Presurgical Randomized MAPLE Trial (CRUK E/06/039)., Clin. Cancer Res.
Li et al., 2008, BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models., Oncogene
Frattini et al., 2013, The integrated landscape of driver genomic alterations in glioblastoma., Nat. Genet.
Gilmer et al., 2008, Impact of common epidermal growth factor receptor and HER2 variants on receptor activity and inhibition by lapatinib., Cancer Res.
Ross et al., 2010, Randomized phase II multicenter trial of two schedules of lapatinib as first- or second-line monotherapy in patients with advanced or metastatic non-small cell lung cancer., Clin. Cancer Res.
Leslie et al., 2012, Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer., Gynecol. Oncol.
Yang et al., 2001, Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy., Crit. Rev. Oncol. Hematol.
Rossi A et al., 2013, Should epidermal growth factor receptor tyrosine kinase inhibitors be considered ideal drugs for the treatment of selected advanced non-small cell lung cancer patients?, Cancer Treat Rev
Mayo C et al., 2012, Pharmacogenetics of EGFR in lung cancer: perspectives and clinical applications., Pharmacogenomics
Van Cutsem et al., 2009, Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer., N. Engl. J. Med.
Vermorken JB et al., 2008, Platinum-based chemotherapy plus cetuximab in head and neck cancer., N Engl J Med
Funke S et al., 2008, Pharmacogenetics in colorectal cancer: a systematic review., Pharmacogenomics
Giusti RM et al., 2008, U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens., Clin Cancer Res
Jonker et al., 2007, Cetuximab for the treatment of colorectal cancer., N. Engl. J. Med.
Bonner JA et al., 2006, Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck., N Engl J Med
Normanno N et al., 2006, Epidermal growth factor receptor (EGFR) signaling in cancer., Gene
Thatcher N et al., 2005, Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)., Lancet
Herbst RS et al., 2004, Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2., J Clin Oncol
Giaccone G et al., 2004, Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1., J Clin Oncol
Jorissen RN et al., 2003, Epidermal growth factor receptor: mechanisms of activation and signalling., Exp Cell Res
Jaiswal et al., 2013, Oncogenic ERBB3 mutations in human cancers., Cancer Cell
Bidard FC et al., 2015, Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer., Ann Oncol
Prickett et al., 2009, Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4., Nat. Genet.
Canfield et al., 2015, Receptor tyrosine kinase ERBB4 mediates acquired resistance to ERBB2 inhibitors in breast cancer cells., Cell Cycle
Davies et al., 2012, Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background., Mol. Cancer Ther.
Dogruluk et al., 2015, Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations., Cancer Res.
Loibl S et al., 2014, PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer., J Clin Oncol
Eichhorn PJ et al., 2008, Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235., Cancer Res
Spraggs CF et al., 2013, Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors., Pharmacogenomics
Chan EC et al., 2012, Interaction of lapatinib with cytochrome P450 3A5., Drug Metab Dispos
Barbara JE et al., 2013, Metabolism-dependent inhibition of CYP3A4 by lapatinib: evidence for formation of a metabolic intermediate complex with a nitroso/oxime metabolite formed via a nitrone intermediate., Drug Metab Dispos
Spraggs CF et al., 2018, Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes., Pharmacogenomics J
Schaid DJ et al., 2014, Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury., J Clin Oncol
Spraggs CF et al., 2011, HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer., J Clin Oncol
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.
Xia et al., 2006, Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers., Cancer Res.
Baumslag, Trace metal studies in Bushman hair., Arch. Environ. Health
Karajannis et al., 2012, Phase II trial of lapatinib in adult and pediatric patients with neurofibromatosis type 2 and progressive vestibular schwannomas., Neuro-oncology
Wilson et al., 2011, Neuregulin-1-mediated autocrine signaling underlies sensitivity to HER2 kinase inhibitors in a subset of human cancers., Cancer Cell
Leung et al., 2015, Combining lapatinib and pertuzumab to overcome lapatinib resistance due to NRG1-mediated signalling in HER2-amplified breast cancer., Oncotarget
Zhao et al., 2014, Mislocalization of p27 to the cytoplasm of breast cancer cells confers resistance to anti-HER2 targeted therapy., Oncotarget

LAPATINIB HLA-DQA1

Interaction Score: 2.28

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24687830 21245432

Sources:
PharmGKB FDA
LAPATINIB EEF2K

Interaction Score: 2.28

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
LAPATINIB ERBB2

Interaction Score: 1.16

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

combination therapy Lapatinib;Chemotherapy

Drug family ERBB2 inhibitor;Chemotherapy

Alteration ERBB2:amp

PMIDs:
2015169 25694417 26243863 22908275 26487584 25435280 27108243 27450453 25221644 27140927 24868024 19786658 27026198 26920887 26245675 25238247 23948973 24971884 27900369 27697991 27197158 26628478 27760111 26296355 22586653 20179222 26432108 27595477 23220880 22046346 18413839 26270481 23940356 18774637 26570998 25305330 24355130 24516025 16397024 26619011 25157968 17192538 16091755 22257673 26811533 22493419 20124187 12214266 16894399 14751502 20110044 20658522 15374980 11752352 14633707 15163842 14737100 14967461 18803986 23122784 19228746 25398453

Sources:
TALC DTC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial JAX-CKB CGI TEND DoCM CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB
LAPATINIB CDH1

Interaction Score: 0.76

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Lapatinib + Capecitabine

Indication/Tumor Type breast cancer

Response Type sensitive

PMIDs:
26487584

Sources:
JAX-CKB
LAPATINIB EGFR

Interaction Score: 0.61

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Prostate

Alteration EGFR:E690K

Drug family ERBB2 inhibitor

PMIDs:
12214266 16894399 14751502 20110044 20658522 15374980 11752352 14633707 15163842 14737100 14967461 18803986 18408761 25305330 24355130 23917401 18199554 20215545 27595477 22885469 11255078 23022519 22594511 19339720 18784101 18681783 18316547 18003960 16467544 16377102 16257339 14990633 14990632 12648464

Sources:
TALC DTC TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB CGI TEND DoCM CIViC GuideToPharmacology CancerCommons PharmGKB TTD OncoKB
LAPATINIB NF2

Interaction Score: 0.57

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration NF2:del

Alteration NF2:.

PMIDs:
973739 22844108

Sources:
CGI
LAPATINIB ABCB11

Interaction Score: 0.57

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23556451

Sources:
PharmGKB
LAPATINIB ERBB3

Interaction Score: 0.53

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status preclinical

Pathway activation

Variant Effect gain-of-function

PMIDs:
23680147 25398453 25953157

Sources:
CGI DoCM CIViC PharmGKB
LAPATINIB ERBB4

Interaction Score: 0.48

Interaction Types & Directionality:

n/a

Interaction Info:

Variant Effect gain-of-function

Pathway activation

Clinical Status preclinical

PMIDs:
19718025 25590338

Sources:
DTC JAX-CKB CGI DoCM CIViC PharmGKB
LAPATINIB CDKN1B

Interaction Score: 0.38

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
25587029

Sources:
CIViC
LAPATINIB NRG1

Interaction Score: 0.38

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration NRG1__.

PMIDs:
21840482 25691057

Sources:
CGI CIViC
LAPATINIB HLA-DRB1

Interaction Score: 0.29

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
28786423 24687830

Sources:
PharmGKB FDA
LAPATINIB PIK3CA

Interaction Score: 0.16

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type no benefit

Approval Status Preclinical - Pdx

Indication/Tumor Type urinary bladder cancer

PMIDs:
22294718 26270481 23940356 26920887 26245675 26627007 25199759 19010894

Sources:
JAX-CKB CIViC PharmGKB
LAPATINIB BIRC5

Interaction Score: 0.13

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16452223

Sources:
NCI
LAPATINIB CCND1

Interaction Score: 0.11

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
LAPATINIB FGFR2

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
27595477

Sources:
JAX-CKB
LAPATINIB MET

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration MET:amp;ERBB2:amp

combination therapy Crizotinib + Lapatinib

PMIDs:
26432108 27595477

Sources:
JAX-CKB CGI
LAPATINIB PGR

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB FDA
LAPATINIB SRC

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Indication/Tumor Type urinary bladder cancer

Response Type no benefit

PMIDs:
26270481

Sources:
JAX-CKB
LAPATINIB BRAF

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy Lapatinib + Panobinostat

Indication/Tumor Type colorectal cancer

PMIDs:
23365119 21464044

Sources:
JAX-CKB
LAPATINIB CYP3A5

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22511346 23404373

Sources:
DTC
LAPATINIB KRAS

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trastuzumab;Lapatinib

Drug family ERBB2 mAb inhibitor;ERBB2 inhibitor

Alteration KRAS:.

PMIDs:
27108243

Sources:
JAX-CKB CGI
LAPATINIB AURKB

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LAPATINIB RET

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LAPATINIB ESR2

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
LAPATINIB ESR1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB FDA
LAPATINIB YES1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LAPATINIB CYP3A4

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22511346

Sources:
DTC

CancerCommons: LAPATINIB
- Version: 25-July-2013
Alternate Names:

208908 PubChem Drug ID

Drug Info:

Drug Class EGFR inhibitor

Source Reported Drug Name(s) Lapatinib

Pharmaceutical Developer GlaxoSmithKline

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

GSK572016 Development Name

GW2016 Development Name

TYKERB Trade Name

Drug Info:

Drug Class Kinase Inhibitors

FDA Approval Breast cancer (HER2+)

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

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small Molecule

FDA Approval approved

Publications:
TEND: LAPATINIB
- Version: 01-August-2011
Alternate Names:

Drug Info:

Drug Class antineoplastic agents, protein kinase inhibitors

Year of Approval 2007

Publications:
NCI: GW572016
- Version: 14-September-2017
Alternate Names:

C26653 NCI drug code

Drug Info:

Publications:

Xia et al., 2006, Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers., Cancer Res.

DTC: LAPATINIB

Version: 02-September-2020

Alternate Names:

CHEMBL554 ChEMBL Drug ID

Drug Info:

Publications:

Barbara JE et al., 2013, Metabolism-dependent inhibition of CYP3A4 by lapatinib: evidence for formation of a metabolic intermediate complex with a nitroso/oxime metabolite formed via a nitrone intermediate., Drug Metab Dispos

Chan EC et al., 2012, Interaction of lapatinib with cytochrome P450 3A5., Drug Metab Dispos

Lyu A et al., 2014, Design and synthesis of Lapatinib derivatives containing a branched side chain as HER1/HER2 targeting antitumor drug candidates., Eur J Med Chem

PharmGKB: lapatinib

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Schaid DJ et al., 2014, Prospective validation of HLA-DRB107:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury., J Clin Oncol

Spraggs CF et al., 2018, Characterisation of the HLA-DRB107:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes., Pharmacogenomics J

Cancer Cell Line Encyclopedia Consortium. et al., 2015, Pharmacogenomic agreement between two cancer cell line data sets., Nature

CGI: Lapatinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Scott et al., 1991, The effects of flosequinan on regional blood flow in normal man., Br J Clin Pharmacol

Lorenzen et al., 2015, Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie., Eur. J. Cancer

Baumslag, Trace metal studies in Bushman hair., Arch. Environ. Health

JAX-CKB: Lapatinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Pan et al., 2015, Development and Characterization of Bladder Cancer Patient-Derived Xenografts for Molecularly Guided Targeted Therapy., PLoS ONE

Secrier et al., 2016, Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance., Nat. Genet.

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

DoCM: LAPATINIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Prickett et al., 2009, Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4., Nat. Genet.

Leslie et al., 2012, Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer., Gynecol. Oncol.

Jaiswal et al., 2013, Oncogenic ERBB3 mutations in human cancers., Cancer Cell

CIViC: LAPATINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Li et al., 2008, BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models., Oncogene

Geyer et al., 2006, Lapatinib plus capecitabine for HER2-positive advanced breast cancer., N. Engl. J. Med.

Xia et al., 2005, Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells., Oncogene

TTD: Lapatinib
- Version: 2020.06.01
Alternate Names:

D08CDI TTD Drug ID

Drug Info:

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

TYKERB Drug Trade Name

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL554
- Version: ChEMBL_27
Alternate Names:

Drug Info:

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

Drug Info:

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

Drug Info:

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

Drug Info:

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

Drug Info:

Publications:
GuideToPharmacology: 178102319
- Version: 29-September-2020
Alternate Names:

Drug Info:

Publications:

combination therapy	Lapatinib;Chemotherapy
Drug family	ERBB2 inhibitor;Chemotherapy
Alteration	ERBB2:amp

combination therapy	Lapatinib + Capecitabine
Indication/Tumor Type	breast cancer
Response Type	sensitive

Reported Cancer Type	Prostate
Alteration	EGFR:E690K
Drug family	ERBB2 inhibitor

Clinical Status	preclinical
Pathway	activation
Variant Effect	gain-of-function

Response Type	no benefit
Approval Status	Preclinical - Pdx
Indication/Tumor Type	urinary bladder cancer

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

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

GSK572016	Development Name
GW2016	Development Name
TYKERB	Trade Name

antagonist (inhibitory)
inhibitor (inhibitory)

antagonist (inhibitory)
inhibitor (inhibitory)

LAPATINIB Drug Record

LAPATINIB chembl:CHEMBL554 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24687830 21245432

Sources: PharmGKB FDA

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: TTD

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

Interaction Info: combination therapy Lapatinib;Chemotherapy Drug family ERBB2 inhibitor;Chemotherapy Alteration ERBB2:amp

Sources: TALC DTC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial JAX-CKB CGI TEND DoCM CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Lapatinib + Capecitabine Indication/Tumor Type breast cancer Response Type sensitive

PMIDs: 26487584

Sources: JAX-CKB

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

Interaction Info: Reported Cancer Type Prostate Alteration EGFR:E690K Drug family ERBB2 inhibitor

Sources: TALC DTC TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB CGI TEND DoCM CIViC GuideToPharmacology CancerCommons PharmGKB TTD OncoKB

Interaction Types & Directionality: n/a

Interaction Info: Drug family ERBB2 inhibitor Alteration NF2:del Alteration NF2:.

PMIDs: 973739 22844108

Sources: CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23556451

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: Clinical Status preclinical Pathway activation Variant Effect gain-of-function

PMIDs: 23680147 25398453 25953157

Sources: CGI DoCM CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: Variant Effect gain-of-function Pathway activation Clinical Status preclinical

PMIDs: 19718025 25590338

Sources: DTC JAX-CKB CGI DoCM CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 25587029

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: Drug family ERBB2 inhibitor Alteration NRG1__.

PMIDs: 21840482 25691057

Sources: CGI CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 28786423 24687830

Sources: PharmGKB FDA

Interaction Types & Directionality: n/a

Interaction Info: Response Type no benefit Approval Status Preclinical - Pdx Indication/Tumor Type urinary bladder cancer

PMIDs: 22294718 26270481 23940356 26920887 26245675 26627007 25199759 19010894

Sources: JAX-CKB CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 16452223

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB

Interaction Types & Directionality: n/a

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

PMIDs: 27595477

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Drug family ERBB2 inhibitor Alteration MET:amp;ERBB2:amp combination therapy Crizotinib + Lapatinib

PMIDs: 26432108 27595477

Sources: JAX-CKB CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB FDA

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Indication/Tumor Type urinary bladder cancer Response Type no benefit

PMIDs: 26270481

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Types & Directionality:

n/a

PMIDs:
24687830 21245432

Sources:
PharmGKB FDA

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
TTD

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

combination therapy Lapatinib;Chemotherapy

Drug family ERBB2 inhibitor;Chemotherapy

Alteration ERBB2:amp

Sources:
TALC DTC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial JAX-CKB CGI TEND DoCM CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Lapatinib + Capecitabine

Indication/Tumor Type breast cancer

Response Type sensitive

PMIDs:
26487584

Sources:
JAX-CKB

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Prostate

Alteration EGFR:E690K

Drug family ERBB2 inhibitor

Sources:
TALC DTC TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB CGI TEND DoCM CIViC GuideToPharmacology CancerCommons PharmGKB TTD OncoKB

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration NF2:del

Alteration NF2:.

PMIDs:
973739 22844108

Sources:
CGI

Interaction Types & Directionality:

n/a

PMIDs:
23556451

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status preclinical

Pathway activation

Variant Effect gain-of-function

PMIDs:
23680147 25398453 25953157

Sources:
CGI DoCM CIViC PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Variant Effect gain-of-function

Pathway activation

Clinical Status preclinical

PMIDs:
19718025 25590338

Sources:
DTC JAX-CKB CGI DoCM CIViC PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
25587029

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration NRG1__.

PMIDs:
21840482 25691057

Sources:
CGI CIViC

Interaction Types & Directionality:

n/a

PMIDs:
28786423 24687830

Sources:
PharmGKB FDA

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type no benefit

Approval Status Preclinical - Pdx

Indication/Tumor Type urinary bladder cancer

PMIDs:
22294718 26270481 23940356 26920887 26245675 26627007 25199759 19010894

Sources:
JAX-CKB CIViC PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
16452223

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
27595477

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration MET:amp;ERBB2:amp

combination therapy Crizotinib + Lapatinib

PMIDs:
26432108 27595477

Sources:
JAX-CKB CGI

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB FDA

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Indication/Tumor Type urinary bladder cancer

Response Type no benefit

PMIDs:
26270481

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy Lapatinib + Panobinostat

Indication/Tumor Type colorectal cancer

PMIDs:
23365119 21464044

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
22511346 23404373

Sources:
DTC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trastuzumab;Lapatinib

Drug family ERBB2 mAb inhibitor;ERBB2 inhibitor

Alteration KRAS:.

PMIDs:
27108243

Sources:
JAX-CKB CGI

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
DTC