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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, PMID: 35324529), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Dec 2023). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK V1180X ALK V1180L |
Transcript | NM_004304.5 |
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_004304.5 | 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 |
NM_004304.4 | chr2:g.29220813C>G | c.3538G>C | p.V1180L | RefSeq | GRCh38/hg38 |
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 | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) 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 | 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 | 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 | 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 | 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 | 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 a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141). | 31446141 |
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 |
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 a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141). | 31446141 |
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 | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 35421578). | 35421578 |
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 | 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 a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141). | 31446141 |
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 | 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 | 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 | sensitive | Iruplinalkib | Preclinical - Cell culture | Actionable | In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK V1180L | large cell neuroendocrine carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK V1180L was identified on post-progression biopsy in a patient with large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20), who previously responded to Alecensa (alectinib) treatment (PMID: 36207130). | 36207130 |
EML4 - ALK ALK V1180L | lung adenocarcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK V1180L was identified at progression on Alecensa (alectinib) in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 34058070). | 34058070 |
EML4 - ALK ALK V1180L | lung adenocarcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK V1180L was identified in the post-progression biopsy of a patient with metastatic lung adenocarcinoma harboring EML4-ALK who progressed on treatment with Alecensa (alectinib) (PMID: 37907052). | 37907052 |
EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK V1180L | lung small cell carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor shrinkage after 5 months, with decrease in the size of intracranial and pulmonary lesions, in a patient with transformed small cell lung cancer from lung adenocarcinoma harboring EML4-ALK and ALK V1180L (PMID: 37907052). | 37907052 |
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 | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK V1180L was identified in 4% (2/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib) treatment (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
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 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 |
EML4 - ALK ALK V1180L ALK G1202R | large cell neuroendocrine carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK developed progressive disease after initial response to Alecensa (alectinib) treatment, post-progression circulating tumor DNA analysis identified the acquisition of ALK V1180L and ALK G1202R, together with TP53 G105V and MYCN E378fs (PMID: 34994612). | 34994612 |
EML4 - ALK ALK V1180L ALK G1202R | large cell neuroendocrine carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations demonstrated further progressive disease 2 weeks after initiating Alunbrig (brigatinib) treatment (PMID: 34994612). | 34994612 |
EML4 - ALK ALK V1180L ALK G1202R | large cell neuroendocrine carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical improvement and regression of lung lesions after 4 weeks of therapy in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations; however, new bone lesions and progression of the brain mass was seen, and significant progressive disease developed after 3 months (PMID: 34994612). | 34994612 |
EML4 - ALK ALK I1171N ALK V1180L | lung adenocarcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK, as well as IDH1 R132H, developed progressive disease after initial response to Alecensa (alectinib), and ALK I1171N and ALK V1180L were identified in the post-progression biopsy along with germline BRCA2 F2801fs (PMID: 35324529). | 35324529 |