Gene Variant Detail

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Gene ALK
Variant V1180L
Impact List missense
Protein Effect unknown
Gene Variant Descriptions ALK V1180L lies within the protein kinase domain of the Alk protein (UniProt.org). V1180L has been demonstrated to occur as a secondary resistance mutation in the context of EML4-ALK (PMID: 25228534, PMID: 27432227), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2021).
Associated Drug Resistance Y

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Transcript NM_004304.4
gDNA chr2:g.29220813C>G
cDNA c.3538G>C
Protein p.V1180L
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304.4 chr2:g.29220813C>G c.3538G>C p.V1180L RefSeq GRCh38/hg38
NM_004304 chr2:g.29220813C>G c.3538G>C p.V1180L RefSeq GRCh38/hg38

Filtering

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK V1180L lung non-small cell carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring ALK V1180L in the context of EML4-ALK was resistant to Xalkori (crizotinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L lung non-small cell carcinoma resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing ALK V1180L in the context of EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis of non-small cell lung carcinoma cells harboring ALK V1180L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK V1180L were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
ALK rearrange ALK V1180L lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical study, ALK V1180L was identified in post-progression biopsies of 2 non-small cell lung cancer patients harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). 29935304
ALK rearrange ALK V1180L lung non-small cell carcinoma predicted - resistant Alectinib Clinical Study - Cohort Actionable In a retrospective study, ALK V1180L was identified in 11% (5/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). 31358542
ALK rearrange ALK V1180L lung non-small cell carcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical study, Alunbrig (brigatinib) treatment resulted in 1 partial response and 1 stable disease in a total of 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK V1180L (PMID: 29935304). 29935304
ALK rearrange ALK V1180L ALK L1196M ALK G1202R lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R and ALK L1196M were identified at disease progression while on Alunbrig (brigatinib) treatment in liquid biopsy of a patient with ALK-positive non-small cell lung cancer also harboring an ALK V1180L (PMID: 29935304). 29935304
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK mutant lung non-small cell carcinoma no benefit Crizotinib + Onalespib Phase II Actionable In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ALK mutant lung non-small cell carcinoma no benefit Belizatinib Phase I Actionable In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). 31217479