DGIdb - TRASTUZUMAB Drug Record

TRASTUZUMAB chembl:CHEMBL1201585 ApprovedAntineoplasticImmunotherapy

Alternate Names:

4D5V8
ABP 980
KADCYLA
DMB-3111 (TRASTUZUMAB BIOSIMILAR)
SYD977
ABP-980
HERCEPTIN
TRASTUZUMAB BETA
R-597
EG-12014
TRASTUZUMAB
SYD-977
EG12014
IG GAMMA-1 CHAIN C REGION
ANTI HER2
chemidplus:180288-69-1
drugbank:00072
chembl:CHEMBL1201585
rxcui:224905

Drug Info:

Drug Class	antineoplastic agents
Year of Approval	1998
FDA Approval	approved
Drug Class	monoclonal antibody
Drug Indications	antineoplastic agent
FDA Approval	Breast cancer (HER2+), Gastric cancer (HER2+)
Drug Class	Therapeutic Antibodies

(13 More Sources)

Publications:

Jaiswal et al., 2013, Oncogenic ERBB3 mutations in human cancers., Cancer Cell
Coté D et al., 2018, Germline single nucleotide polymorphisms in ERBB3 and BARD1 genes result in a worse relapse free survival response for HER2-positive breast cancer patients treated with adjuvant based docetaxel, carboplatin and trastuzumab (TCH)., PLoS One
Bidard FC et al., 2015, Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer., Ann Oncol
Bose et al., 2013, Activating HER2 mutations in HER2 gene amplification negative breast cancer., Cancer Discov
Lee et al., 2006, Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas., Clin. Cancer Res.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
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.
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
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.
Ring et al., 2015, Phase I Study to Assess the Combination of Afatinib with Trastuzumab in Patients with Advanced or Metastatic HER2-Positive Breast Cancer., Clin. Cancer Res.
Takashima et al., 2014, Phase II study of S-1 in combination with trastuzumab for HER2-positive metastatic breast cancer., Anticancer Res.
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.
Blumenthal et al., 2013, First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer., Clin. Cancer Res.
André et al., 2014, Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial., Lancet Oncol.
Bartsch et al., 2007, Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer., J. Clin. Oncol.
Ding et al., 2014, Trastuzumab and oxaliplatin exhibit a synergistic antitumor effect in HER2-postive gastric cancer cells., Anticancer Drugs
Bachelot et al., 2014, Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer: activity and safety results from a phase II study., BMC Cancer
Berns et al., 2007, A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer., Cancer Cell
Wang et al., 2011, PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib., BMC Cancer
Saura et al., 2014, Phase Ib study of Buparlisib plus Trastuzumab in patients with HER2-positive advanced or metastatic breast cancer that has progressed on Trastuzumab-based therapy., 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
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.
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.
Hamad et al., 2017, Neoadjuvant Treatment With Trastuzumab and FOLFOX Induces a Complete Pathologic Response in a Metastatic ERBB2 (HER2)-Amplified Duodenal Cancer., J Natl Compr Canc Netw
Xiao et al., 2016, A Potent HER3 Monoclonal Antibody That Blocks Both Ligand-Dependent and -Independent Activities: Differential Impacts of PTEN Status on Tumor Response., Mol. Cancer Ther.
Finn et al., 2009, PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro., Breast Cancer Res.
Kodack et al., 2017, The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation., Sci Transl Med
Leto et al., 2015, Sustained Inhibition of HER3 and EGFR Is Necessary to Induce Regression of HER2-Amplified Gastrointestinal Carcinomas., Clin. Cancer Res.
Borley et al., 2014, Impact of HER2 copy number in IHC2+/FISH-amplified breast cancer on outcome of adjuvant trastuzumab treatment in a large UK cancer network., Br. J. Cancer
Bang et al., 2010, Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial., Lancet
Tanaka et al., 2011, The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations., Clin. Cancer Res.
Kwak et al., 2015, Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer., Cancer Discov
Chuang et al., 2017, ERBB2-Mutated Metastatic Non-Small Cell Lung Cancer: Response and Resistance to Targeted Therapies., J Thorac Oncol
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.
Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE
Espelin et al., 2016, Dual HER2 Targeting with Trastuzumab and Liposomal-Encapsulated Doxorubicin (MM-302) Demonstrates Synergistic Antitumor Activity in Breast and Gastric Cancer., Cancer Res.
Lin et al., 2007, The role of trastuzumab in early stage breast cancer: current data and treatment recommendations., Curr Treat Options Oncol
Levêque et al., 2008, Clinical pharmacology of trastuzumab., Curr Clin Pharmacol
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Treish et al., 2000, Pharmacology and therapeutic use of trastuzumab in breast cancer., Am J Health Syst Pharm
Minuti et al., 2012, Increased MET and HGF gene copy numbers are associated with trastuzumab failure in HER2-positive metastatic breast cancer., Br. J. Cancer
Bookman et al., 2003, Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group., J. Clin. Oncol.
McAlpine et al., 2009, HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy., BMC Cancer
Fleming et al., 2010, Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study., Gynecol. Oncol.
Diver et al., 2015, The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer., Oncologist
Doi et al., 2015, Phase 1 pharmacokinetic study of the oral pan-AKT inhibitor MK-2206 in Japanese patients with advanced solid tumors., Cancer Chemother. Pharmacol.
Chlebowski et al., 1976, Metallophosphoryl and Apophosphoryl Alkaline Phosphatases., J. Biol. Chem.
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.
Andre et al., 2010, Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab., J. Clin. Oncol.
Jerusalem et al., 2011, Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer., Breast Cancer Res. Treat.
1998, Pharmacogenomics at work., Nat Biotechnol
Beauclair S et al., 2007, Role of the HER2 [Ile655Val] genetic polymorphism in tumorogenesis and in the risk of trastuzumab-related cardiotoxicity., Ann Oncol
Stemmler et al., 2006, Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer., Oncol. Rep.
Altundag et al., 2004, Adjuvant targeted therapy with trastuzumab may decrease metastatic capacity in specific group of oropharyngeal cancer patients: downregulation of E-cadherin-catenin complex by cooperative effect of erbB-2 and human papillomavirus type 16 E6/E7 protooncogenes., Med. Hypotheses
Sharon E et al., 2010, Sustained response of carcinoma ex pleomorphic adenoma treated with trastuzumab and capecitabine., Head Neck Oncol
Mazières et al., 2016, Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort., Ann. Oncol.
Yarlagadda B et al., 2019, Trastuzumab and pertuzumab in circulating tumor DNA ERBB2-amplified HER2-positive refractory cholangiocarcinoma., NPJ Precis Oncol
Meric-Bernstam F et al., 2019, Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study., Lancet Oncol
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
Chakrabarty et al., 2013, Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors., Cancer Res.
Baselga et al., 2012, Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial., Lancet
Baselga et al., 2012, Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer., N. Engl. J. Med.
von Minckwitz et al., 2009, Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study., J. Clin. Oncol.
Piccart-Gebhart et al., 2005, Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer., N. Engl. J. Med.
Chan et al., 2016, Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial., Lancet Oncol.
Santin et al., 2008, Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu., Int J Gynaecol Obstet
Swain et al., 2015, Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer., N. Engl. J. Med.
Kinehara et al., 2015, Favorable response to trastuzumab plus irinotecan combination therapy in two patients with HER2-positive relapsed small-cell lung cancer., Lung Cancer
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.
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.
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
Marty et al., 2005, Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group., J. Clin. Oncol.
Slamon et al., 2001, Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2., N. Engl. J. Med.
Hirotsu et al., 2017, Intrinsic HER2 V777L mutation mediates resistance to trastuzumab in a breast cancer patient., Med. Oncol.
Martin M et al., 2017, Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial., Lancet Oncol
Singh H et al., 2018, U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer., Clin Cancer Res
Fader AN et al., 2018, Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu., J Clin Oncol
Takahashi H et al., 2019, Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Salivary Duct Carcinoma., J Clin Oncol
Varchetta et al., 2007, Elements related to heterogeneity of antibody-dependent cell cytotoxicity in patients under trastuzumab therapy for primary operable breast cancer overexpressing Her2., Cancer Res.
Tamura K et al., 2011, FcγR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer., Ann Oncol
Musolino A et al., 2008, Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer., J Clin Oncol
Suzuki et al., 2007, A nonfucosylated anti-HER2 antibody augments antibody-dependent cellular cytotoxicity in breast cancer patients., Clin. Cancer Res.
Razis E et al., 2011, Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer., Breast Cancer Res Treat
O'Brien et al., 2010, Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models., Clin. Cancer Res.
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.
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
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.
Fujita et al., 2006, PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer., Br. J. Cancer
Nagata et al., 2004, PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients., Cancer Cell
Esteva et al., 2010, PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer., Am. J. Pathol.
Grell et al., 2012, Akt expression and compartmentalization in prediction of clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab., Int. J. Oncol.
Prang et al., 2005, Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines., Br. J. Cancer
Zhang et al., 2007, FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab., J. Clin. Oncol.
Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov
Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov
Parihar et al., 2004, A phase I study of interleukin 12 with trastuzumab in patients with human epidermal growth factor receptor-2-overexpressing malignancies: analysis of sustained interferon gamma production in a subset of patients., Clin. Cancer Res.
Xia et al., 2006, Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers., Cancer Res.

TRASTUZUMAB FCGR2A

Interaction Score: 2.52

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
21109570 18347005 17704420 17016423 17139284

Sources:
PharmGKB
TRASTUZUMAB RNF8

Interaction Score: 1.96

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
30071039

Sources:
PharmGKB
TRASTUZUMAB ERBB2

Interaction Score: 1.84

Interaction Types & Directionality:

antibody (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Receptor protein-tyrosine kinase erbB-2 inhibitor

Notes

PMIDs:
23220880 16397024 25157968 26243863 26619011 22908275 27626067 27108243 25370464 24982373 27140927 23801166 24742739 17679724 24300914 24606768 17936563 21676217 24470511 26245675 27697991 23948973 28784859 26880266 19874578 28539475 26296355 24691421 20728210 21558396 26432108 28167203 23940356 26469692 26759238 17660958 18690878 11752352 11098307 22850551 12525520 20003286 19840887 26099744 26104654 2605 2013 20975068 21107682 9788323 30071039 17693647 16596213 15236790 20504363 26598547 31453370 30857956 29320312 23204226 22257673 22149875 19289619 16236737 26874901 18555254 25693012 25601188 20124187 22493419 16091755 15911866 11248153 27900589 29146401 29523624 29584549 30452336

Sources:
TALC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions NCI DoCM CIViC PharmGKB TTD FDA OncoKB
TRASTUZUMAB BARD1

Interaction Score: 1.18

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
30071039

Sources:
PharmGKB
TRASTUZUMAB EPCAM

Interaction Score: 0.74

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15655555

Sources:
NCI
TRASTUZUMAB FCGR3A

Interaction Score: 0.74

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
18089830 21109570 18347005 17363544

Sources:
NCI PharmGKB
TRASTUZUMAB PPCDC

Interaction Score: 0.74

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
TRASTUZUMAB ERBB3

Interaction Score: 0.59

Interaction Types & Directionality:

n/a

Interaction Info:

Variant Effect gain-of-function

Pathway activation

Clinical Status preclinical

PMIDs:
23680147 30071039 25953157

Sources:
DoCM CIViC PharmGKB
TRASTUZUMAB PIK3CA

Interaction Score: 0.35

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trastuzumab + Lapatinib

Indication/Tumor Type Her2-receptor positive breast cancer

Response Type decreased response

PMIDs:
21594665 20453058 22294718 25199759 28167203 21558396 23940356 21676217 17936563 24470511 26469692 26245675 19010894 26920887

Sources:
JAX-CKB CIViC PharmGKB
TRASTUZUMAB IFNG

Interaction Score: 0.35

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15297404

Sources:
NCI
TRASTUZUMAB BIRC5

Interaction Score: 0.33

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23204226 16452223

Sources:
NCI CIViC
TRASTUZUMAB APC

Interaction Score: 0.31

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

PMIDs:
27626067

Sources:
JAX-CKB
TRASTUZUMAB AKT2

Interaction Score: 0.27

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22842582

Sources:
CIViC
TRASTUZUMAB PTEN

Interaction Score: 0.24

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Clinical Study

Response Type decreased response

Evidence Type Actionable

PMIDs:
21676217 17936563 24470511 16404430 15324695 20813970

Sources:
JAX-CKB CIViC
TRASTUZUMAB PGR

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB FDA
TRASTUZUMAB MET

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy Crizotinib + Trastuzumab + Paclitaxel

combination therapy Trastuzumab + Fluorouracil + Leucovorin + Oxaliplatin

PMIDs:
26432108 22850551

Sources:
JAX-CKB
TRASTUZUMAB KRAS

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Neratinib + Trastuzumab

Indication/Tumor Type colorectal cancer

Response Type resistant

PMIDs:
27108243 26243863

Sources:
JAX-CKB
TRASTUZUMAB BRAF

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

PMIDs:
27626067

Sources:
JAX-CKB
TRASTUZUMAB ESR2

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
TRASTUZUMAB EGFR

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11752352

Sources:
TEND
TRASTUZUMAB ESR1

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB FDA

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

TRASTUZUMAB Primary Drug Name

Drug Info:

Year of Approval 1998

Drug Class antineoplastic agents

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

TRASTUZUMAB Generic Name

HERCEPTIN Trade Name

Drug Info:

Drug Class Therapeutic Antibodies

FDA Approval Breast cancer (HER2+), Gastric cancer (HER2+)

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

Drug Info:

Drug Indications antineoplastic agent

Drug Class monoclonal antibody

FDA Approval approved

Publications:

NCI: TRASTUZUMAB

Version: 14-September-2017

Alternate Names:

C1647 NCI drug code

Drug Info:

Publications:

Varchetta et al., 2007, Elements related to heterogeneity of antibody-dependent cell cytotoxicity in patients under trastuzumab therapy for primary operable breast cancer overexpressing Her2., Cancer Res.

Prang et al., 2005, Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines., Br. J. Cancer

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

JAX-CKB: Trastuzumab

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Berns et al., 2007, A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer., Cancer Cell

Wang et al., 2011, PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib., BMC Cancer

Saura et al., 2014, Phase Ib study of Buparlisib plus Trastuzumab in patients with HER2-positive advanced or metastatic breast cancer that has progressed on Trastuzumab-based therapy., Clin. Cancer Res.

DoCM: TRASTUZUMAB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

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

Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.

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.

PharmGKB: trastuzumab

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Coté D et al., 2018, Germline single nucleotide polymorphisms in ERBB3 and BARD1 genes result in a worse relapse free survival response for HER2-positive breast cancer patients treated with adjuvant based docetaxel, carboplatin and trastuzumab (TCH)., PLoS One

Musolino A et al., 2008, Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer., J Clin Oncol

Tamura K et al., 2011, FcγR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer., Ann Oncol

CIViC: TRASTUZUMAB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Hirotsu et al., 2017, Intrinsic HER2 V777L mutation mediates resistance to trastuzumab in a breast cancer patient., Med. Oncol.

Sharon E et al., 2010, Sustained response of carcinoma ex pleomorphic adenoma treated with trastuzumab and capecitabine., Head Neck Oncol

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: Trastuzumab
- Version: 2020.06.01
Alternate Names:

D04WFL TTD Drug ID

Drug Info:

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

TRASTUZUMAB Primary Drug Name

TRASTUZUMAB Drug Generic Name

HERCEPTIN Drug Trade Name

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL1201585
- Version: ChEMBL_27
Alternate Names:

Drug Info:

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

Drug Info:

Publications:
JAX-CKB: trastuzumab
- Version: 27-September-2017
Alternate Names:

Drug Info:

Publications:
ChemblInteractions: CHEMBL1201585
- Version: chembl_23
Alternate Names:

Drug Info:

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

Drug Info:

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

Drug Info:

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

Drug Info:

Publications:

Direct Interaction	yes
Mechanism of Interaction	Receptor protein-tyrosine kinase erbB-2 inhibitor
Notes

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

combination therapy	Trastuzumab + Lapatinib
Indication/Tumor Type	Her2-receptor positive breast cancer
Response Type	decreased response

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

Approval Status	Clinical Study
Response Type	decreased response
Evidence Type	Actionable

Response Type	sensitive
combination therapy	Crizotinib + Trastuzumab + Paclitaxel
combination therapy	Trastuzumab + Fluorouracil + Leucovorin + Oxaliplatin

combination therapy	Neratinib + Trastuzumab
Indication/Tumor Type	colorectal cancer
Response Type	resistant

TRASTUZUMAB	Primary Drug Name
TRASTUZUMAB	Drug Generic Name
HERCEPTIN	Drug Trade Name

antibody (inhibitory)
inhibitor (inhibitory)

TRASTUZUMAB Drug Record

TRASTUZUMAB chembl:CHEMBL1201585 ApprovedAntineoplasticImmunotherapy

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 21109570 18347005 17704420 17016423 17139284

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 30071039

Sources: PharmGKB

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

Interaction Info: Direct Interaction yes Mechanism of Interaction Receptor protein-tyrosine kinase erbB-2 inhibitor Notes

Sources: TALC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions NCI DoCM CIViC PharmGKB TTD FDA OncoKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 30071039

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 15655555

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 18089830 21109570 18347005 17363544

Sources: NCI PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB

Interaction Types & Directionality: n/a

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

PMIDs: 23680147 30071039 25953157

Sources: DoCM CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Trastuzumab + Lapatinib Indication/Tumor Type Her2-receptor positive breast cancer Response Type decreased response

PMIDs: 21594665 20453058 22294718 25199759 28167203 21558396 23940356 21676217 17936563 24470511 26469692 26245675 19010894 26920887

Sources: JAX-CKB CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 15297404

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23204226 16452223

Sources: NCI CIViC

Interaction Types & Directionality: n/a

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

PMIDs: 27626067

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 22842582

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: Approval Status Clinical Study Response Type decreased response Evidence Type Actionable

PMIDs: 21676217 17936563 24470511 16404430 15324695 20813970

Sources: JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB FDA

Interaction Types & Directionality: n/a

Interaction Info: Response Type sensitive combination therapy Crizotinib + Trastuzumab + Paclitaxel combination therapy Trastuzumab + Fluorouracil + Leucovorin + Oxaliplatin

PMIDs: 26432108 22850551

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Neratinib + Trastuzumab Indication/Tumor Type colorectal cancer Response Type resistant

PMIDs: 27108243 26243863

Sources: JAX-CKB

Interaction Types & Directionality: n/a

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

PMIDs: 27626067

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
21109570 18347005 17704420 17016423 17139284

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
30071039

Sources:
PharmGKB

Interaction Types & Directionality:

antibody (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Receptor protein-tyrosine kinase erbB-2 inhibitor

Notes

Sources:
TALC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions NCI DoCM CIViC PharmGKB TTD FDA OncoKB

Interaction Types & Directionality:

n/a

PMIDs:
30071039

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
15655555

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
18089830 21109570 18347005 17363544

Sources:
NCI PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Variant Effect gain-of-function

Pathway activation

Clinical Status preclinical

PMIDs:
23680147 30071039 25953157

Sources:
DoCM CIViC PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trastuzumab + Lapatinib

Indication/Tumor Type Her2-receptor positive breast cancer

Response Type decreased response

PMIDs:
21594665 20453058 22294718 25199759 28167203 21558396 23940356 21676217 17936563 24470511 26469692 26245675 19010894 26920887

Sources:
JAX-CKB CIViC PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
15297404

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
23204226 16452223

Sources:
NCI CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

PMIDs:
27626067

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
22842582

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Clinical Study

Response Type decreased response

Evidence Type Actionable

PMIDs:
21676217 17936563 24470511 16404430 15324695 20813970

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB FDA

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy Crizotinib + Trastuzumab + Paclitaxel

combination therapy Trastuzumab + Fluorouracil + Leucovorin + Oxaliplatin

PMIDs:
26432108 22850551

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Neratinib + Trastuzumab

Indication/Tumor Type colorectal cancer

Response Type resistant

PMIDs:
27108243 26243863

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

PMIDs:
27626067

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
11752352

Sources:
TEND

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB FDA

Alternate Names:

TRASTUZUMAB Primary Drug Name

Drug Info:

Year of Approval 1998

Drug Class antineoplastic agents

Alternate Names:

TRASTUZUMAB Generic Name

HERCEPTIN Trade Name

Drug Info:

Drug Class Therapeutic Antibodies

FDA Approval Breast cancer (HER2+), Gastric cancer (HER2+)

Drug Info:

Drug Indications antineoplastic agent

Drug Class monoclonal antibody

FDA Approval approved

Alternate Names:

C1647 NCI drug code

Alternate Names:

D04WFL TTD Drug ID

Alternate Names:

TRASTUZUMAB Primary Drug Name

TRASTUZUMAB Drug Generic Name

HERCEPTIN Drug Trade Name