Publication

Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK.

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Cancer Med2015PMID 25727400PMC4529334stubpubmedPublished

Abstract

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Linked entities

Linked entities (11)

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 11

cancerMalignant Neoplasmcivic_curation1.00
drugAlectinibcivic_curation1.00
drugBrigatinibcivic_curation1.00
drugCeritinibcivic_curation1.00
drugCrizotinibcivic_curation1.00
geneALKcivic_curation1.00
variantALK Fusioncivic_curation1.00
variantALK Fusioncivic_curation1.00
variantALK Fusioncivic_curation1.00
variantALK G1202Rcivic_curation1.00
variantALK G1269Acivic_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 G1269A + ALK Fusion3
Alectinib	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	3	accepted	EID1354 EML4-ALK with ALK G1269A mutation was tested for sensitivity to alectinib using Ba/F3 cells. In Ba/F3 cells with ectopic EML4-ALK variant 1 G1269A, IC50 of 84 nM was reported with alectinib, which was… (full text at CIViC) PMID 25727400 · Fontana et al., 2015 · Open in CIViC	civic
Brigatinib	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1353 EML4-ALK with ALK G1269A has been seen in crizotinib resistant NSCLC, and this mutation was tested for Brigatinib sensitivity via ectopic expression in Ba/F3 cells, where half maximal inhibitory conce… (full text at CIViC) PMID 25727400 · Fontana et al., 2015 · Open in CIViC	civic
Ceritinib	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1355 EML4-ALK with G1269A mutation was tested for sensitivity to ceritinib via transduction into Ba/F3 cells and generation of survival curves varying ceritinib concentration. IC50 of 33 nM was seen, which… (full text at CIViC) PMID 25727400 · Fontana et al., 2015 · Open in CIViC	civic
ALK G1202R + ALK Fusion2
Alectinib	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	3	accepted	EID1350 Ba/F3 cell line expressing EML4-ALK variant 3 with G1202R ALK mutation was assessed for alectinib sensitivity and IC50 for survival of 868 nM was reported, which was 64.4x higher than the IC50 reporte… (full text at CIViC) PMID 25727400 · Fontana et al., 2015 · Open in CIViC	civic
Brigatinib	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	3	accepted	EID1351 This study compared drug responses in Ba/F3 cells expressing either EML4-ALK or NPM-ALK fusions, with or without G1202R ALK mutation. Cells expressing the EML4-ALK variant 3 with G1202R ALK mutation w… (full text at CIViC) PMID 25727400 · Fontana et al., 2015 · Open in CIViC	civic
ALK Fusion1
Crizotinib	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1356 In Ba/F3 cells, crizotinib sensitivty of the NPM-ALK variant was compared to crizotinib sensitivity of EML4-ALK variant 3. 50% of maximal inhibitory concentration for NPM-ALK was 42 nM, which was appr… (full text at CIViC) PMID 25727400 · Fontana et al., 2015 · Open in CIViC	civic