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Profile Name | ALK F1174C |
Gene Variant Detail | |
Relevant Treatment Approaches | ALK Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK F1174C | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | conflicting | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were sensitive to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | conflicting | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated sensitivity to Alecensa (alectinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition by Alecensa (alectinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK D1203N | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK F1174C ALK D1203N | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK F1174C ALK D1203N | Advanced Solid Tumor | decreased response | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK F1174C ALK D1203N | Advanced Solid Tumor | decreased response | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227). | 27432227 |
EML4 - ALK ALK F1174C ALK D1203N | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK F1174C | lung non-small cell carcinoma | resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who developed resistance to Xalkori (crizotinib) treatment was subsequently treated with Zykadia (ceritinib), eventually progressed, and was found to have acquired ALK F1174C (PMID: 24675041). | 24675041 |
EML4 - ALK ALK C1156Y ALK F1174C | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
EML4 - ALK ALK F1174C ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174C 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 |
EML4 - ALK ALK F1174C ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
ALK rearrange ALK F1174C | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). | 31358542 |
ALK rearrange ALK F1174C ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). | 31439588 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | conflicting | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated decreased sensitivity to Alecensa (alectinib) in culture compared to cells expressing EML4-ALK with wild-type ALK (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | conflicting | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C | 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 F1174C in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK F1174C | 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 F1174C in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK F1174C ALK E1210K | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, ALK F1174C, and ALK E1210K (PMID: 34378333). | 34378333 |
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A | lung adenocarcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A were identified in the post-progression biopsy of a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e13:e20), who previously responded to Xalkori (crizotinib) treatment (PMID: 36093526). | 36093526 |
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 10 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A (PMID: 36093526). | 36093526 |
EML4 - ALK ALK F1174C | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease lasting 6 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C, who previously progressed on Xalkori (crizotinib) and Alunbrig (brigatinib) (PMID: 36093526). | 36093526 |
EML4 - ALK ALK F1174C ALK L1196M | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C, who previously responded to Lorbrena (lorlatinib) treatment (PMID: 36093526). | 36093526 |
EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to TPX-0131 in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). | 36201110 |
ALK F1174C TP53 wild-type | neuroblastoma | resistant | Idasanutlin + Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model of TP53 wild-type neuroblastoma harboring ALK F1174C was resistant to combination treatment with Lorbrena (lorlatinib) and Idasanutlin (RG7388) (PMID: 36602782). | 36602782 |
EML4 - ALK ALK F1174C | 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 F1174C in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK F1174C | lung adenocarcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) progressed on treatment with Xalkori (crizotinib) and was found to have acquired ALK F1174C (PMID: 38978737). | 38978737 |
EML4 - ALK ALK F1174C | lung adenocarcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response and a progression-free survival of 29 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK F1174C (PMID: 38978737). | 38978737 |
EML4 - ALK ALK F1174C 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 (e6:e20) and ALK F1174C progressed on treatment with Alecensa (alectinib) and was found to have acquired ALK V1180L (PMID: 38978737). | 38978737 |
EML4 - ALK ALK F1174C ALK V1180L | lung adenocarcinoma | predicted - sensitive | Bevacizumab + Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Lorbrena (lorlatinib) and Avastin (bevacizumab) resulted in a partial response and a progression-free survival of 33 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK F1174C and V1180L (PMID: 38978737). | 38978737 |
EML4 - ALK ALK F1174C ALK G1202R | lung adenocarcinoma | sensitive | NVL-655 | Case Reports/Case Series | Actionable | In a Phase I trial (ALKOVE-1), NVL-655 treatment resulted in a partial response with treatment ongoing for at least 9 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK with ALK G1202R and F1174C in cis (PMID: 39269178; NCT05384626). | 39269178 |
EML4 - ALK ALK F1174C | lung adenocarcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Alecensa (alectinib) treatment resulted in a partial response with a progression-free survival of 13.4 months, overall survival of 25.9 months, and a duration of treatment of 14.5 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C (PMID: 39500140). | 39500140 |