Publication

Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers.

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Sci Transl Med2012PMID 22277784PMC3385512stubpubmedPublished

Abstract

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Linked entities

Linked entities (14)

How each link was made (MeSH, dictionary, registry reference, curation…) and whether it has been validated. Candidate links are not counted in entity statistics.

Validated 14

cancerLung Adenocarcinomacivic_curation1.00
cancerLung Non-Small Cell Carcinomacivic_curation1.00
drugAlectinibcivic_curation1.00
drugALK Inhibitor TAE684civic_curation1.00
drugCrizotinibcivic_curation1.00
drugTanespimycincivic_curation1.00
geneALKcivic_curation1.00
variantALK Amplificationcivic_curation1.00
variantALK Fusioncivic_curation1.00
variantALK Fusioncivic_curation1.00
variantALK G1202Rcivic_curation1.00
variantALK L1196Mcivic_curation1.00
variantALK S1206Ycivic_curation1.00
variantALK T1151dupcivic_curation1.00

Curated evidence

Evidence citing this paper (10)

civicCuratedShowing 1–10 of 10 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
ALK G1202R + ALK Fusion1
Crizotinib	Lung Adenocarcinoma	Predictive	C	Supports Resistance	3	accepted	EID1357 A patient with ALK-rearranged lung adenocarcinoma responded to crizotinib treatment and then had relapse. Biopsy was taken within half a month and total DNA was extracted from the sample. Exons 20-28,… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
ALK Amplification + ALK Fusion1
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID440 Amplification of wild-type EML4-ALK in the non-small cell lung carcinoma cell line, H3122, caused resistance to crizotinib. PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
ALK G1202R + ALK Fusion2
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	4	accepted	EID441 The G1202R mutation in the EML4-ALK fusion was found to confer resistance to crizotinib in Ba/F3 cells. PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
Tanespimycin	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID1352 The G1202R ALK mutation was found in a crizotinib-resistant ALK-rearranged NSCLC, and the mutant ALK fusion was further characterized in Ba/F3 cells. EML4-ALK variant 1 with G1202R mutation was expres… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
ALK L1196M + ALK Fusion1
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	4	accepted	EID442 The L1196M mutation in the EML4-ALK fusion was found to confer resistance to crizotinib in Ba/F3 cells. PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
ALK S1206Y + ALK Fusion1
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	4	accepted	EID443 The S1206Y mutation in the EML4-ALK fusion was found to confer resistance to crizotinib in Ba/F3 cells. PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
ALK T1151dup + ALK Fusion4
Alectinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID1347 Ba/F3 cells expressing EML4-ALK with 1151 Tins treated with alectinib had an IC50 of 165.7 nM, 16x higher than those expressing EML4-ALK wildtype variant 1. EML4-ALK variant 1 expressing H3122 NSCLC c… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
ALK Inhibitor TAE684	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID1348 Treatment of Ba/F3 cells expressing EML4-ALK 1151 insT with TAE684 produced an IC50 value (28.3 nM) 20x higher cells expressing EML4-ALK wildtype variant 1. The crizotinib resistant clones were produc… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	4	accepted	EID444 A lung adenocarcinoma patient responded to crizotinib treatment for 12 months, after which the cancer relapsed and sequencing of the ALK tyrosine kinase domain revealed a 1151insT mutation. This mutat… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
Tanespimycin	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID1349 Ba/F3 cells transduced with EML4-ALK 1151 insT were treated with 17-AAG producing an IC50 value of 44.5 nM, which was 0.4 times that reported for EML4-ALK wildtype in Ba/F3, indicating possible increa… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic