Publication

Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants.

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Clin Cancer Res2012PMID 22912387stubpubmedPublished

Abstract

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Linked entities

Linked entities (7)

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 7

cancerLung Non-Small Cell Carcinomacivic_curation1.00
drugAlvespimycincivic_curation1.00
drugCrizotinibcivic_curation1.00
geneALKcivic_curation1.00
variantALK e20::e20civic_curation1.00
variantALK e6::e20civic_curation1.00
variantALK Fusioncivic_curation1.00

Curated evidence

Evidence citing this paper (6)

civicCuratedShowing 1–6 of 6 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 e20::e202
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID1196 EML4-ALK variants v1 (E13;A20), v2 (E20;A20), v3a (E6;A20) and v3b (E6ins33;A20) were expressed in Ba/F3 cells using retrovirus. While all constructs rendered Ba/F3 cells IL3-independant, marked diff… (full text at CIViC) PMID 22912387 · Heuckmann et al., 2012 · Open in CIViC	civic
Alvespimycin + CrizotinibCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID1204 EML4-ALK fusions occur in 2-7% of lung adenocarcinomas. Transduction of Ba/F3 cells with EML4-ALK variant 2 (EML4 exon 20 fused to ALK exon 20) caused the cells to grow independently of IL3 addition. … (full text at CIViC) PMID 22912387 · Heuckmann et al., 2012 · Open in CIViC	civic
ALK e6::e202
Alvespimycin	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Does Not Support Sensitivity Response	2	accepted	EID1205 Transduction of Ba/F3 cells with EML4-ALK variant 3a caused the cells to grow independently of IL3 addition. While incubation of Ba/F3 cells transduced with EML4-ALK variants 1 and 2 with Hsp90 inhib… (full text at CIViC) PMID 22912387 · Heuckmann et al., 2012 · Open in CIViC	civic
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Does Not Support Sensitivity Response	2	accepted	EID1197 Ba/F3 cells transduced with EML4-ALK variants v1 (E13;A20), v2 (E20;A20), v3a (E6;A20) and v3b (E6ins33;A20) showed differential sensitivity to both crizotinib and TAE684, with variant 3a (E6;A20) bei… (full text at CIViC) PMID 22912387 · Heuckmann et al., 2012 · Open in CIViC	civic
ALK Fusion1
Alvespimycin + CrizotinibCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID1206 Transduction of Ba/F3 cells with EML4-ALK variant 1 causes IL3 independent growth. Incubation of EML4-ALK variant 1 transduced Ba/F3 cells with Hsp90 inhibitor 17-DMAG caused cell death that was rever… (full text at CIViC) PMID 22912387 · Heuckmann et al., 2012 · Open in CIViC	civic
ALK Fusion1
Crizotinib	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	rejected	EID1268 Different ALK fusions were compared for crizotinib sensitivity using the Ba/F3 cell model. In Ba/F3 cells, AK fusions capable of acting as cancer drivers will cause IL3 independent growth, and ALK inh… (full text at CIViC) PMID 22912387 · Heuckmann et al., 2012 · Open in CIViC	civic