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Chemical: Drug
erlotinib

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Prescribing Info (0) Drug Labels (4) Clinical Annotations (7)

PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.

Annotated Labels

Annotation of FDA Label for erlotinib and EGFR
Annotation of EMA Label for erlotinib and EGFR,UGT1A1
Annotation of PMDA Label for erlotinib and EGFR
Annotation of HCSC Label for erlotinib and EGFR

last updated 10/25/2013

1. Annotation of FDA Label for erlotinib and EGFR

On FDA Biomarker List

Testing required

Summary

TARCEVA (erlotinib) is a kinase inhibitor indicated for First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

There's more of this label. Read more.

last updated 10/25/2013

2. Annotation of EMA Label for erlotinib and EGFR,UGT1A1

Testing required

Summary

The EMA European Public Assessment Report (EPAR) requires testing tumours for EGFR mutations in patients with non-small cell lung cancer prior to treatment with erlotinib and recommends using a well-validated method of testing. The drug should be used with caution in patients with low expression of UGT1A1 or Gilbert's disease (caused by genetic variants in UGT1A1 gene), due to the inhibitory effects of erlotinib on glucuronidation by UGT1A1 (UGT1A1 genetic testing is not required).

There's more of this label. Read more.

3. Annotation of PMDA Label for erlotinib and EGFR

Testing required

Summary

The PMDA package insert for erlotinib states that it is indicated for recurrent and/or advanced inoperable non-small cell lung cancer that is positive for an EGFR gene mutation and has not been previously treated with chemotherapy.

There's more of this label. Read more.

4. Annotation of HCSC Label for erlotinib and EGFR

Testing required

Summary

The product monograph for erlotinib (TARCEVA) states that it is indicated for patients with non-small cell lung cancer (NSCLC) who have a confirmed activating EGFR mutation.

There's more of this label. Read more.

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Clinical Annotation for rs121434568 (EGFR), erlotinib and Carcinoma, Non-Small-Cell Lung (level 1B Efficacy)

Level of Evidence: Level 1B
Type: Efficacy
Variant: rs121434568
Genes: EGFR
Phenotypes: Carcinoma, Non-Small-Cell Lung
OMB Race: Unknown

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs121434569 (EGFR), erlotinib, gefitinib and Carcinoma, Non-Small-Cell Lung (level 2A Efficacy)

Level of Evidence: Level 2A
Type: Efficacy
Variant: rs121434569
Genes: EGFR
Phenotypes: Carcinoma, Non-Small-Cell Lung
OMB Race: Unknown

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs121434568 (EGFR), carboplatin, docetaxel, erlotinib, gemcitabine, paclitaxel and Carcinoma, Non-Small-Cell Lung (level 2A Efficacy)

Level of Evidence: Level 2A
Type: Efficacy
Variant: rs121434568
Genes: EGFR
Phenotypes: Carcinoma, Non-Small-Cell Lung
OMB Race: Unknown

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs726501 (MAP3K1), carboplatin, cisplatin, docetaxel, erlotinib, gefitinib and paclitaxel (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: rs726501
Genes: MAP3K1
OMB Race: Mixed Population

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs712829 (EGFR), erlotinib and Neoplasms (level 3 Toxicity/ADR)

Level of Evidence: Level 3
Type: Toxicity/ADR
Variant: rs712829
Genes: EGFR
Phenotypes: Neoplasms
OMB Race: Unknown

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs2472304 (CYP1A2), erlotinib (level 3 Metabolism/PK)

Level of Evidence: Level 3
Type: Metabolism/PK
Variant: rs2472304
Genes: CYP1A2
OMB Race: Asian
Race Notes: Korean

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs712829 (EGFR), erlotinib and Neoplasms (level 4 Efficacy)

Level of Evidence: Level 4
Type: Efficacy
Variant: rs712829
Genes: EGFR
Phenotypes: Neoplasms
Race: NCI-60 cell lines
Race Notes: NCI-60 cell lines

To see the rest of this clinical annotation please register or sign in.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for erlotinib

	Gene ?	Variant? (147)	Alternate Names ?	Chemicals ?	Alleles ? (+ chr strand)	Function ?	Amino Acid? Translation
VA	ABCB1	*2 (PMID: 11503014)		erlotinib	N/A	N/A	N/A
VA	CYP2D6	*1		erlotinib	N/A	N/A	N/A
VA	CYP2D6	*2		erlotinib	N/A	N/A	N/A
VA	CYP2D6	*10		erlotinib	N/A	N/A	N/A
VA	CYP2D6	*14A		erlotinib	N/A	N/A	N/A
VA	CYP3A4	*1B		erlotinib	N/A	N/A	N/A
CA VA	EGFR	rs121434568	NC_000007.13:g.55259515T>G, NC_000007.14:g.55191822T>G, NG_007726.3:g.177791T>G, NM_005228.3:c.2573T>G, NP_005219.2:p.Leu858Arg, XM_005271746.1:c.2438T>G, XM_005271747.1:c.2414T>G, XP_005271803.1:p.Leu813Arg, XP_005271804.1:p.Leu805Arg	carboplatin gemcitabine paclitaxel docetaxel gefitinib erlotinib	T > G	SNP	L858R
CA VA	EGFR	rs121434569	NC_000007.13:g.55249071C>T, NC_000007.14:g.55181378C>T, NG_007726.3:g.167347C>T, NM_005228.3:c.2369C>T, NP_005219.2:p.Thr790Met, NR_047551.1:n.1193G>A, XM_005271746.1:c.2234C>T, XM_005271747.1:c.2210C>T, XP_005271803.1:p.Thr745Met, XP_005271804.1:p.Thr737Met	gefitinib erlotinib	C > T	SNP	T790M
VA	MET	rs2237717	NC_000007.13:g.116405387T>C, NC_000007.14:g.116765333T>C, NG_008996.1:g.97929T>C, NM_000245.2:c.2583+2065T>C, NM_001127500.1:c.2637+2065T>C, XM_005250353.1:c.2694+2065T>C, XM_005250354.1:c.1293+2065T>C, XM_006715990.2:c.1293+2065T>C, XM_006715991.2:c.1293+2065T>C, XM_011516223.1:c.2640+2065T>C, rs10360329, rs56649045, rs60573720	erlotinib	T > C	SNP
CA VA	CYP1A2	rs2472304	NC_000015.10:g.74751897G>A, NC_000015.9:g.75044238G>A, NG_008431.1:g.34356G>A, NM_000761.3:c.1042+43G>A, NM_000761.4:c.1042+43G>A, rs17419193, rs17861158, rs3743483, rs58648468	erlotinib	G > A	SNP
VA	ABCG2	rs2622604	NC_000004.11:g.89078924T>C, NC_000004.12:g.88157772T>C, NG_032067.2:g.78551A>G, NM_001257386.1:c.-19-17758A>G, NM_004827.2:c.-20+614A>G, XM_005263354.1:c.-20+805A>G, XM_005263354.2:c.-20+805A>G, XM_005263355.1:c.-19-17758A>G, XM_005263355.2:c.-19-17758A>G, XM_005263356.1:c.-20+614A>G, XM_005263356.2:c.-20+614A>G, XM_011532420.1:c.-19-17758A>G, rs61481684	erlotinib	T > A T > C	SNP
CA VA	EGFR	rs712829	NC_000007.13:g.55086755G>T, NC_000007.14:g.55019062G>T, NG_007726.3:g.5031G>T, NM_005228.3:c.-216G>T, NM_201282.1:c.-216G>T, NM_201283.1:c.-216G>T, NM_201284.1:c.-216G>T, XM_005271746.1:c.-216G>T, XM_005271748.1:c.-216G>T, rs17288931	erlotinib	G > T	SNP
CA	MAP3K1	rs726501	NC_000005.10:g.56832039G>A, NC_000005.9:g.56127866G>A, NG_031884.1:g.21967G>A, NM_005921.1:c.482+15984G>A, XM_005248519.1:c.71+11223G>A, XM_005248519.3:c.104+11223G>A, XM_005248520.1:c.-8+14923G>A, XM_011543406.1:c.227+15704G>A, XM_011543407.1:c.482+15984G>A, XM_011543408.1:c.482+15984G>A, rs57031684	carboplatin cisplatin docetaxel paclitaxel gefitinib erlotinib	G > A	SNP
VA	CYP3A5	rs776746	NC_000007.13:g.99270539C>T, NC_000007.14:g.99672916T>C, NG_007938.1:g.12083G=, NG_007938.1:g.12083G>A, NM_000777.4:c.219-237A>G, NM_000777.4:c.219-237G>A, NM_001190484.2:c.219-237A>G, NM_001190484.2:c.219-237G>A, NM_001291829.1:c.-253-1A>G, NM_001291829.1:c.-253-1G>A, NM_001291830.1:c.189-237A>G, NM_001291830.1:c.189-237G>A, NR_033807.2:n.717-1A>G, NR_033807.2:n.717-1G>A, NR_033808.1:n.689-1G>A, NR_033809.1:n.581-237G>A, NR_033810.1:n.689-1G>A, NR_033811.1:n.321-1G>A, NR_033812.1:n.321-1G>A, XM_005250169.1:c.189-237G>A, XM_005250170.1:c.-357-1G>A, XM_005250171.1:c.-253-1G>A, XM_005250172.1:c.-254G>A, XM_005250173.1:c.-331-237G>A, XM_005250198.1:c.806-4288C>T, XM_006715859.2:c.219-237A>G, XM_011515843.1:c.-254A>G, XM_011515844.1:c.-229-237A>G, XM_011515845.1:c.-463-1A>G, XM_011515846.1:c.-331-237A>G, XM_011515847.1:c.-571-1A>G, XR_927383.1:n.344-237A>G, XR_927402.1:n.1466+48736T>C, rs10361242, rs11266830, rs386613022, rs58244770	erlotinib	C > T	SNP

Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

2D structure from PubChem

[ see larger image ] [ see 3D structure ]

provided by PubChem

Overview

Generic Names

OSI-774

Trade Names

Tarceva

Brand Mixture Names

PharmGKB Accession Id

PA134687924

Type(s):

Drug

Description

Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.

Source: Drug Bank

Pharmacogenetics

There are two kinds of mutations in EGFR that influence efficacy of erlotinib:

Mutations that increase drug sensitivity such as L858R (rs121434568) and exon 19 deletions. These are somatic gain-of-function mutations that are cancer-driving and activate EGFR, making it more sensitive to tyrosine kinase inhibitors, TKIs, such as erlotinib. These are discussed further in the EGFR VIP gene summary.

Secondary mutations that result in aquired resistance to TKIs including T790M (rs121434569) [Article:15737014]. These are also discussed further in the EGFR VIP gene summary.

Source: PharmGKB [Article:23962910] [Article:15737014]

Indication

For the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Also for use, in combination with gemcitabine, as the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.

Source: Drug Bank

Other Vocabularies

MeSH: erlotinib (C400278)
ATC: Protein kinase inhibitors (L01XE)
UMLS: erlotinib (C1135135)
RxNorm: erlotinib (337525)
NDFRT: ERLOTINIB (N0000148872)

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.

Source: Drug Bank

Pharmacology

Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/Epidermal Growth Factor Receptor (HER1/EGFR) tyrosine kinase inhibitor.

Source: Drug Bank

Food Interaction

Take with a glass of water.|Take at least 1 hour before or 2 hours after any food.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

In vitro assays of cytochrome P450 metabolism showed that erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1.

Source: Drug Bank

Protein Binding

93% protein bound to albumin and alpha-1 acid glycoprotein (AAG)

Source: Drug Bank

Absorption

Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%.

Source: Drug Bank

Half-Life

Median half-life of 36.2 hours.

Source: Drug Bank

Toxicity

Symptoms of overdose include diarrhea, rash, and liver transaminase elevation.

Source: Drug Bank

Chemical Properties

Chemical Formula

C22H23N3O4

Source: Drug Bank

Average Molecular Weight

393.4357

Source: Drug Bank

Monoisotopic Molecular Weight

393.168856239

Source: Drug Bank

SMILES

COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC

Source: PubChem

InChI String

InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)

Source: PubChem

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

EGFR Inhibitor Pathway, Pharmacodynamics
Model non-tissue specific cancer cell displaying genes that may be involved in the treatment using epidermal growth factor receptor specific tyrosine kinase inhibitors or monoclonal antibodies.

Erlotinib Pathway, Pharmacokinetics
Model human liver cell showing genes involved in the transportation and metabolism of Erlotinib.

Related Genes and Targets Related Drugs and Interactions Related Diseases/Phenotypes

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Evidence	Gene
VA VIP PW	ABCB1
VA PW	ABCG2
PW	CYP1A1
DL CA VA PW	CYP1A2
PW	CYP2C8
VA	CYP2D6
DL VA PW	CYP3A4
VA PW	CYP3A5
DL CA VA VIP PW	EGFR
PW	ERBB2
PW	ERBB3
PW	ERBB4
CA	MAP3K1
VA	MET
DL PW	UGT1A1

Drug Targets

Gene	Description
EGFR	(source: Drug Bank )

Drug Interactions

Interaction	Description
atazanavir - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
atazanavir - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
clarithromycin - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
clarithromycin - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
erythromycin - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
erythromycin - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
indinavir - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
indinavir - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
itraconazole - erlotinib	This potent CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
itraconazole - erlotinib	This potent CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
ketoconazole - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
ketoconazole - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
nefazodone - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
nefazodone - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
nelfinavir - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
nelfinavir - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
rifabutin - erlotinib	Decreased levels/effect of erlotinib (source: Drug Bank )
rifabutin - erlotinib	Decreased levels/effect of erlotinib (source: Drug Bank )
rifampin - erlotinib	Decreased levels/effect of erlotinib (source: Drug Bank )
rifampin - erlotinib	Decreased levels/effect of erlotinib (source: Drug Bank )
telithromycin - erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank )
telithromycin - erlotinib	Telithromycin may reduce clearance of Erlotinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Erlotinib if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
trastuzumab - erlotinib	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank )
voriconazole - erlotinib	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of erlotinib by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of erlotinib if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank )

Curated Information ?

Evidence	Disease
VA	Adenocarcinoma
DL CA VA	Carcinoma, Non-Small-Cell Lung
VA	Diarrhea
VA	Drug Resistance
VA	Drug Toxicity
VA	Exanthema
DL VA	Lung Neoplasms
DL CA VA	Neoplasms
DL VA	Pancreatic Neoplasms
	Smoke Inhalation Injury

Publications related to erlotinib: 96

	Targeting therapeutic liabilities engendered by PIK3R1 mutations for cancer treatment. Pharmacogenomics. 2016. Cheung Lydia Wt, et al.
CA VA	Comparison of clinical outcomes of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations after tyrosine kinase inhibitors treatment: a meta-analysis. European journal of clinical pharmacology. 2015. Sheng Miaomiao, et al.
	Pharmacogenomics in the treatment of lung cancer: an update. Pharmacogenomics. 2015. Morales-Espinosa Daniela, et al.
CA VA	Pharmacokinetic properties of two erlotinib 150 mg formulations with a genetic effect evaluation in healthy Korean subjects. Clinical drug investigation. 2015. Choi Hyun-Gyu, et al.
	In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug metabolism and disposition: the biological fate of chemicals. 2014. Filppula Anne M, et al.
	EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, et al.
	Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors. Drug metabolism and drug interactions. 2014. Khurana Varun, et al.
	Clinical Implementation of Germline Cancer Pharmacogenetic Variants during the Next-Generation Sequencing Era. Clinical pharmacology and therapeutics. 2013. Gillis Nancy K, et al.
	The integrated landscape of driver genomic alterations in glioblastoma. Nature genetics. 2013. Frattini Veronique, et al.
	Emerging landscape of oncogenic signatures across human cancers. Nature genetics. 2013. Ciriello Giovanni, et al.
VIP	PharmGKB summary: very important pharmacogene information for the epidermal growth factor receptor. Pharmacogenetics and genomics. 2013. Hodoglugil Ugur, et al.
	Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al.
CA VA	Impact of Systematic EGFR and KRAS Mutation Evaluation on Progression-Free Survival and Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Treated by Erlotinib in a French Prospective Cohort (ERMETIC Project-Part 2). Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2012. Cadranel Jacques, et al.
CA VA	Efficacy of EGFR tyrosine kinase inhibitors for non-adenocarcinoma NSCLC patients with EGFR mutation. Cancer chemotherapy and pharmacology. 2012. Cho Su-Hee, et al.
	Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy. The pharmacogenomics journal. 2012. Savonarola A, et al.
VA	Association of ABCB1 polymorphisms with erlotinib pharmacokinetics and toxicity in Japanese patients with non-small-cell lung cancer. Pharmacogenomics. 2012. Hamada Akinobu, et al.
CA VA	Plasma epidermal growth factor receptor mutation analysis and possible clinical applications in pulmonary adenocarcinoma patients treated with erlotinib. Oncology letters. 2012. Chen Yuh-Min, et al.
CA VA	Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. The lancet oncology. 2012. Rosell Rafael, et al.
CA VA	Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012. Su Kang-Yi, et al.
VA	Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer. BMC cancer. 2012. Suzumura Tomohiro, et al.
	Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity. The pharmacogenomics journal. 2011. Parmar S, et al.
CA VA	Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011. Brugger Wolfram, et al.
CA VA	A noninvasive system for monitoring resistance to epidermal growth factor receptor tyrosine kinase inhibitors with plasma DNA. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2011. Nakamura Tomomi, et al.
CA VA	Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. The lancet oncology. 2011. Zhou Caicun, et al.
VA	Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer. Pancreas. 2011. Zeng Hongmei, et al.
CA	Genetic variations in multiple drug action pathways and survival in advanced stage non-small cell lung cancer treated with chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Li Yafei, et al.
	A phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus. Cancer. 2011. Ilson David H, et al.
CA VA	Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Rosell Rafael, et al.
CA VA	Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Arcila Maria E, et al.
VIP	Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al.
CA VA	Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Science translational medicine. 2011. Sequist Lecia V, et al.
	Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al.
	Pharmacogenetic tests in cancer chemotherapy: what physicians should know for clinical application. The Journal of pathology. 2011. Lee Soo-Youn, et al.
	Use of epidermal growth factor receptor mutation analysis in patients with advanced non-small-cell lung cancer to determine erlotinib use as first-line therapy. PLoS currents. 2011. Ishibe Naoko, et al.
	Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al.
	The UGT1A128 polymorphism correlates with erlotinib's effect on SN-38 glucuronidation. European journal of cancer (Oxford, England : 1990).* 2010. Liu Yong, et al.
	Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clinical pharmacology and therapeutics. 2010. Stegmeier F, et al.
CA	Acquired resistance to gefitinib: the contribution of mechanisms other than the T790M, MET, and HGF status. Lung cancer (Amsterdam, Netherlands). 2010. Onitsuka Takamitsu, et al.
CA VA	Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer cell. 2010. Turke Alexa B, et al.
	Comparison of the drug-drug interactions potential of erlotinib and gefitinib via inhibition of UDP-glucuronosyltransferases. Drug metabolism and disposition: the biological fate of chemicals. 2010. Liu Yong, et al.
CA VA	Clinicopathologic and molecular features of epidermal growth factor receptor T790M mutation and c-MET amplification in tyrosine kinase inhibitor-resistant Chinese non-small cell lung cancer. Pathology oncology research : POR. 2009. Chen Hua-Jun, et al.
	Grb7 upregulation is a molecular adaptation to HER2 signaling inhibition due to removal of Akt-mediated gene repression. PloS one. 2010. Nencioni Alessio, et al.
	The increasing role of pharmacogenetics in the treatment of gastrointestinal cancers. Gastrointestinal cancer research : GCR. 2009. Yalçin Suayib.
CA VA	Screening for epidermal growth factor receptor mutations in lung cancer. The New England journal of medicine. 2009. Rosell Rafael, et al.
VIP	Influx and efflux transport as determinants of melphalan cytotoxicity: Resistance to melphalan in MDR1 overexpressing tumor cell lines. Biochemical pharmacology. 2009. Kühne Annett, et al.
	Clinically available pharmacogenomics tests. Clinical pharmacology and therapeutics. 2009. Flockhart D A, et al.
VIP	Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Hauswald Stefanie, et al.
CA	Prospective phase II study of gefitinib in non-small cell lung cancer with epidermal growth factor receptor gene mutations. Lung cancer (Amsterdam, Netherlands). 2009. Sugio Kenji, et al.
VIP	Genetic determinants of response to clopidogrel and cardiovascular events. The New England journal of medicine. 2009. Simon Tabassome, et al.
VIP	Cost-effectiveness of 99mTc-sestamibi in predicting response to chemotherapy in patients with lung cancer: systematic review and meta-analysis. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2009. Mohan Hosahalli K, et al.
VIP	Induction of multiple drug transporters by efavirenz. Journal of pharmacological sciences. 2009. Weiss Johanna, et al.
VIP	Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities. Antioxidants & redox signaling. 2009. Kuo Macus Tien.
VIP	Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008. Luna-Tortós Carlos, et al.
CA	Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008. Costa Daniel B, et al.
CA VA	Detection of mutations in EGFR in circulating lung-cancer cells. The New England journal of medicine. 2008. Maheswaran Shyamala, et al.
VIP	Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhou S-F.
CA VA	Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008. Miller Vincent A, et al.
CA VA	Pharmacogenomic and pharmacokinetic determinants of erlotinib toxicity. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008. Rudin Charles M, et al.
VIP	Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008. Uhr Manfred, et al.
VIP	Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacological research : the official journal of the Italian Pharmacological Society. 2008. Nikisch Georg, et al.
CA VA	Impact of EGFR gene polymorphisms on anticancer drug cytotoxicity in vitro. Molecular diagnosis & therapy. 2008. Puyo Stéphane, et al.
CA VA	MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proceedings of the National Academy of Sciences of the United States of America. 2007. Bean James, et al.
	MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science (New York, N.Y.). 2007. Engelman Jeffrey A, et al.
VIP	Tariquidar (XR9576): a P-glycoprotein drug efflux pump inhibitor. Expert review of anticancer therapy. 2007. Fox Elizabeth, et al.
	Association of variant ABCG2 and the pharmacokinetics of epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients. Cancer biology & therapy. 2007. Li Jing, et al.
CA VA	Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing. The oncologist. 2007. Sequist Lecia V, et al.
VIP	Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2007. Marguerite Véronique, et al.
VIP	Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. Molecular pharmaceutics. 2007. Collnot Eva-Maria, et al.
CA VA	Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Balak Marissa N, et al.
CA	Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Kosaka Takayuki, et al.
CA	Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer research. 2006. Inukai Michio, et al.
VIP	Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer research. 2006. Leggas Markos, et al.
VIP	Impact of P-glycoprotein on clopidogrel absorption. Clinical pharmacology and therapeutics. 2006. Taubert Dirk, et al.
	Effects of smoking on the pharmacokinetics of erlotinib. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Hamilton Marta, et al.
	Metabolism and excretion of erlotinib, a small molecule inhibitor of epidermal growth factor receptor tyrosine kinase, in healthy male volunteers. Drug metabolism and disposition: the biological fate of chemicals. 2006. Ling Jie, et al.
VIP	Single nucleotide polymorphisms in human P-glycoprotein: its impact on drug delivery and disposition. Expert opinion on drug delivery. 2006. Dey Surajit.
CA	Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nature genetics. 2005. Bell Daphne W, et al.
CA VA	Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005. Eberhard David A, et al.
CA VA	Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS medicine. 2005. Pao William, et al.
	EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proceedings of the National Academy of Sciences of the United States of America. 2004. Pao William, et al.
	The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004. Perez-Soler Roman.
VIP	Influence of lipid lowering fibrates on P-glycoprotein activity in vitro. Biochemical pharmacology. 2004. Ehrhardt Manuela, et al.
VIP	Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharmaceutical research. 2004. Hochman Jerome H, et al.
VIP	Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clinical pharmacology and therapeutics. 2004. Marzolini Catia, et al.
	Targeting the epidermal growth factor receptor in non-small cell lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2003. Herbst Roy S, et al.
	Specific method for determination of OSI-774 and its metabolite OSI-420 in human plasma by using liquid chromatography-tandem mass spectrometry. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2003. Zhao Ming, et al.
VIP	Genetic polymorphisms of the human MDR1 drug transporter. Annual review of pharmacology and toxicology. 2003. Schwab Matthias, et al.
VIP	Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn-Schmiedeberg's archives of pharmacology. 2001. Pauli-Magnus C, et al.
VIP	The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. The Journal of clinical investigation. 1999. Greiner B, et al.
VIP	Anti-psychotic drugs reverse multidrug resistance of tumor cell lines and human AML cells ex-vivo. Cancer letters. 1999. Szabó D, et al.
VIP	Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annual review of pharmacology and toxicology. 1999. Ambudkar S V, et al.
VIP	Increased systemic toxicity of sarcoma chemotherapy due to combination with the P-glycoprotein inhibitor cyclosporin. International journal of clinical pharmacology and therapeutics. 1998. Theis J G, et al.
VIP	Competitive, non-competitive and cooperative interactions between substrates of P-glycoprotein as measured by its ATPase activity. Biochimica et biophysica acta. 1997. Litman T, et al.
VIP	MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell. 1996. van Helvoort A, et al.
VIP	Synergistic reversal of multidrug-resistance phenotype in acute myeloid leukemia cells by cyclosporin A and cremophor EL. Blood. 1994. Ross D D, et al.
VIP	P-glycoprotein structure and evolutionary homologies. Cytotechnology. 1993. Croop J M.

LinkOuts

Web Resource:: Wikipedia
DrugBank:: DB00530
PDB:: AQ4
ChEBI:: 114785

PubChem Compound:: 176870
PubChem Substance:: 46508021; 7885946
Drugs Product Database (DPD):: 2269023
BindingDB:: 5446

ChemSpider:: 154044
HET:: AQ4
Therapeutic Targets Database:: DAP001010

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