Publication

The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.

Authors not recorded

Cancer Discov2014PMID 24675041PMC4068971stubpubmedPublished

Abstract

Abstract (excerpt)

Only the opening of the abstract is shown; abstract text may carry publisher copyright.

Data not yet available

No abstract stored. Read on PubMed

Linked entities

Linked entities (13)

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 13

cancerLung Non-Small Cell Carcinomacivic_curation1.00
drugCeritinibcivic_curation1.00
drugCrizotinibcivic_curation1.00
geneALKcivic_curation1.00
variantALK C1156Ycivic_curation1.00
variantALK e6::e20civic_curation1.00
variantALK Fusioncivic_curation1.00
variantALK Fusioncivic_curation1.00
variantALK G1202Rcivic_curation1.00
variantALK G1269Acivic_curation1.00
variantALK I1171civic_curation1.00
variantALK L1196Mcivic_curation1.00
variantALK S1206Ycivic_curation1.00

Curated evidence

Evidence citing this paper (14)

civicCuratedShowing 1–14 of 14 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 F1174C1
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4430 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK F1174C co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK G1269A + ALK Fusion1
Ceritinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID1342 The NSCLC cell line MGH021-4, harboring SQSTM1-ALK G1269A, was 6 times more sensitive to ceritinib (80nM GI50) than crizotinib (500 nM) in proliferation assays and caused notable reductions in phospho… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK I11712
Ceritinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	accepted	EID1344 Ba/F3 cells expressing EML4-ALK variant 3 with ALK I1171T mutation were treated with ceritinib, and survival IC50 of 2.6 nM was observed, which compares favorably with highly ceritinib sensitive EML4-… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4611 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK I1171T co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK L1152P1
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4613 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK L1152P co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK e6::e201
Ceritinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID1340 Ceritinib was 28x more potent (GI50 3.8nM) than crizotinib (GI50 107nM) at inhibiting growth of H2228, an NSCLC cell line which harbors the EML4-ALK variant 3a/3b. SCID mice xenografted with H2228 we… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK C1156Y + ALK Fusion1
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	4	accepted	EID1346 EML4-ALK variant 3 containing NSCLC cell line H2228 xenografts in SCID beige mice were treated with increasing doses of crizotinib up to 100 mg/kg per day by oral gavage. At approximately 40 days tumo… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK G1202R + ALK Fusion2
Ceritinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	4	accepted	EID1345 Ba/F3 cells expressing EML4-ALK variant 1 with ALK G1202R mutation were assessed for ceritinib sensitivity. Crizotinib was shown to confer significantly more potency than ceritinib (43-fold decrease i… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	1	submitted	EID4625 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK G1202R co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK G1269A + ALK Fusion1
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	2	submitted	EID4619 In a non-small cell lung cancer patient with acquired crizotinib resistance, the tumor had an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK G1269A co-mutation. … (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK L1196M + ALK Fusion1
Ceritinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	accepted	EID1341 The crizotinib-resistant MGH045 cell line with EML4-ALK L1196M was treated with crizotinib or ceritinib. In nude mice with MGH045 xenografts, tumor response to crizotinib did not differ appreciably fr… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK S1206Y + ALK Fusion2
Ceritinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID1343 Ba/F3 cells expressing the EML4-ALK S1206Y variant were treated with ceritinib, and survival GI50 value of 1.5 nM was obtained, which compares favorably with GI50 of 1.7 for the highly ceritinib sensi… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	2	submitted	EID4622 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK S1206Y co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
ALK T1151dup + ALK Fusion1
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	2	submitted	EID4608 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK T1151_L1152insT co-mutation, demonstrated resistance to crizotinib treatme… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic