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Gene | ALK |
Variant | I1171S |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | ALK I1171S lies within the protein kinase domain of the Alk protein (UniProt.org). I1171S has been demonstrated to confer drug resistance in the context of ALK fusions in culture (PMID: 27009859, PMID: 25393796, PMID: 26464158), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2020). |
Associated Drug Resistance | Y |
Transcript | NM_004304.4 |
gDNA | chr2:g.29222347A>C |
cDNA | c.3512T>G |
Protein | p.I1171S |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.4 | chr2:g.29222347A>C | c.3512T>G | p.I1171S | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29222347A>C | c.3512T>G | p.I1171S | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796). | 31943796 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | decreased response | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 demonstrated reduced growth inhibition of transformed cells expressing ALK I1171S in the context of EML4-ALK in culture (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | resistant | AZD3463 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796). | 31943796 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | resistant | ASP3026 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK I1171S | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer initially responded to Alecensa (alectinib), but progressed with the emergence of a secondary ALK I1171S mutation (PMID: 25393796). | 25393796 |
NPM1 - ALK ALK I1171S | Advanced Solid Tumor | resistant | ASP3026 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
NPM1 - ALK ALK I1171S | Advanced Solid Tumor | sensitive | AZD3463 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing NPM1-ALK with ALK I1171S in culture (PMID: 27009859). | 27009859 |
NPM1 - ALK ALK I1171S | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
NPM1 - ALK ALK I1171S | anaplastic large cell lymphoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK I1161S were resistant to Xalkori (crizotinib) in culture (PMID: 27009859). | 27009859 |
NPM1 - ALK ALK I1171S | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK I1171S in culture (PMID: 27009859). | 27009859 |
NPM1 - ALK ALK I1171S | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
NPM1 - ALK ALK I1171S | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK I1171S ALK F1174V | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK F1174V initially responded to Alecensa (alectinib), but then demonstrated progression in one of two lung nodules, which was found to harbor a secondary resistance mutation, ALK I1171S, and upon resection of the nodule the patient continued Alecensa (alectinib) treatment and achieved complete remission (PMID: 26464158). | 26464158 |
EML4 - ALK ALK I1171S ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
ALK I1171S ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569). | 31628085 |
EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796). | 31943796 |
EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Xalkori (crizotinib) treatment in culture (PMID: 31943796). | 31943796 |
EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Alecensa (alectinib) treatment in culture (PMID: 31943796). | 31943796 |
EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796). | 31943796 |
EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Lorbrena (lorlatinib) treatment in culture (PMID: 31943796). | 31943796 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
ALK I1171S | unknown | |
EML4 - ALK ALK I1171S | Lorlatinib | |
NPM1 - ALK ALK I1171S | AZD3463 Brigatinib | |
EML4 - ALK ALK I1171S ALK F1174V | ||
EML4 - ALK ALK I1171S ALK L1196M | ||
ALK I1171S ALK pos | ||
EML4 - ALK ALK I1171S ALK G1269A |