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Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib.

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Clin Cancer Res2014PMID 25228534PMC4233168stubpubmedProvenance
Source
PubMed
Retrieved
Sep 8, 2026
Layer
normalized (units and labels harmonized; values unchanged)
Run
ING-CIVIC-20260908-000001
Published

Abstract

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Linked entities

Linked entities (10)

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 10

Curated evidence

Evidence citing this paper (9)

civicProvenance
Source
CIViC — Clinical Interpretation of Variants in Cancer
Dataset
CIViC evidence items
Version
civic-2026-09-08
Retrieved
Sep 8, 2026
Layer
normalized (units and labels harmonized; values unchanged)
Evidence
expert curation
License
CC0 1.0
PMID
25228534
Run
ING-CIVIC-20260908-000001
Open at source
CuratedShowing 1–9 of 9 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.
TherapyCancerTypeLevelDirection · significanceRating (1–5)StatusEvidenceSource
ALK I11714
AlectinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveCSupports Resistance4accepted
EID1283

The I1171T mutation in ALK fusions was found in a NSCLC patient shown positive for ALK rearrangement via break apart FISH assay, who progressed after 8 months of crizotinib, and then progressed again … (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic
ALK Inhibitor TAE684Lung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Sensitivity Response3accepted
EID1285

The I1171T ALK kinase domain mutaion was found in the MGH056-1 cell line which was derived from an ALK rearranged NSCLC patient who had progressed on crizotinib and then on alectinib given at lower do… (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic
CeritinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveCSupports Sensitivity Response4accepted
EID1284

The MGH056-1 cell line was derived from an NSCLC patient with ALK-rearrangement who had progressed on crizotinib and then on alectinib. the cell line was also resistant to crizotinib and alectinib, an… (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic
CrizotinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Resistance3accepted
EID1287

The MGH056-1 cell line was derived from a patient with ALK rearranged NSCLC who had progressed on crizotinib and then on lower dose alectinib (300 mg twice daily). The I1171T ALK kinase domain mutatio… (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic
ALK V1180L + ALK Fusion5
AlectinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Resistance3accepted
EID1286

The EML4 ALK variant 1 containing NSCLC cell line H3122 is highly sensitive to alectinib, and an alectinib resistant derivative cell line H3122 CHR-A1 was generated by incubation of H3122 in increasin… (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic
ALK Inhibitor TAE684Lung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Sensitivity Response3accepted
EID1290

The V1180L mutation in the kinase domain of rearranged ALK was found in an alectinib resistant cell line named H3122 CHR-A1, which was derived from the alectinib sensitive EML4-ALK variant 1 containin… (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic
BrigatinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Sensitivity Response2accepted
EID1291

ALK mutation V1180L was found in an H3122 derivative cell line that had become alectinib resistant after being passaged in increasing levels of alectinib. EML4-ALK V1180L and EML4-ALK wild-type were e… (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic
CeritinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Sensitivity Response3accepted
EID1289

Passaging of the alectinib sensitive EML4-ALK containing H3122 NSCLC cell line with increasing levels of alectinib resulted in an alectinib resistant derivative of this cell line named H3122 CHR-A1. A… (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic
CrizotinibLung Non-Small Cell CarcinomaCURATED_BROADERPredictiveDSupports Resistance2accepted
EID1288

The alectinib resistant cell line H3122 CHR-A1 was generated by culturing of the EML4-ALK (variant 1) containing cell line H3122 with increasing levels of alectinib. Molecular characterization of H312… (full text at CIViC)

PMID 25228534 · Katayama et al., 2014 · Open in CIViC

civic