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Profile Name | ALK F1174L |
Gene Variant Detail | |
Relevant Treatment Approaches | ALK Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
ALK F1174L | Advanced Solid Tumor | sensitive | ALK Inhibitor | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK F1174L was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
ALK F1174L | neuroblastoma | conflicting | ALK Inhibitor | Crizotinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1174L in culture, and only delayed tumor growth in patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). | 26554404 |
ALK F1174L | neuroblastoma | conflicting | ALK Inhibitor | Lorlatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). | 26554404 |
ALK F1174L | Advanced Solid Tumor | sensitive | ALK Inhibitor | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1174L in culture (PMID: 26554404). | 26554404 |
ALK F1174L | neuroblastoma | sensitive | ALK Inhibitor | CEP-28122 | Preclinical - Cell culture | Actionable | In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture (PMID: 22203728). | 22203728 |
ALK F1174L | neuroblastoma | sensitive | ALK Inhibitor | AZD3463 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD3463 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture, resulted in near complete tumor regression in cell line xenograft models (PMID: 26786851). | 26786851 |
ALK F1174L | neuroblastoma | conflicting | ALK Inhibitor | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, neuroblastoma cells harboring ALK F1174L were resistant to Lorbrena (lorlatinib) in culture (PMID: 30322862). | 30322862 |
ALK F1174L | neuroblastoma | conflicting | ALK Inhibitor | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although all 3 patients harboring ALK F1174L had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770). | 33568345 |
ALK F1174L | neuroblastoma | no benefit | ALK Inhibitor | Crizotinib + Cyclophosphamide + Topotecan | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan resulted in progressive disease within 1 cycle of therapy in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1174L and PIK3CA C692Ffs*8 (PMID: 34210658). | 34210658 |
ALK F1174L | neuroblastoma | conflicting | ALK Inhibitor | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting 13 mo in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1174L and PIK3CA C692Ffs*8, who had previously progressed on combination therapy with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan (PMID: 34210658). | 34210658 |
ALK F1174L | Advanced Solid Tumor | predicted - sensitive | ALK Inhibitor | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174L in an in vitro assay (PMID: 34158340). | 34158340 |
ALK F1174L | neuroblastoma | sensitive | Vandetanib | Preclinical | Actionable | In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK F1174L (corresponds to F1178L in mouse) and subsequent upregulation of Ret (PMID: 24811913). | 24811913 | |
ALK F1174L | neuroblastoma | predicted - sensitive | ALK Inhibitor | Entrectinib | Case Reports/Case Series | Actionable | In a Phase I/II trial, Rozlytrek (entrectinib) treatment resulted in a complete response in a patient with neuroblastoma harboring ALK F1174L (PMID: 35395680; NCT02650401). | 35395680 |
ALK F1174L | neuroblastoma | conflicting | ALK Inhibitor | Crizotinib | Case Reports/Case Series | Actionable | In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in stable disease lasting 19 months in a patient with advanced neuroblastoma harboring ALK F1174L (PMID: 29352732; NCT00939770). | 29352732 |
ALK F1174L | neuroblastoma | sensitive | ALK Inhibitor | TQ-B3139 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of a neuroblastoma cell line harboring ALK F1174L in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922). | 30210922 |
ALK F1174L | neuroblastoma | sensitive | ALK Inhibitor | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Repotrectinib (TPX-0005) inhibited proliferation of a neuroblastoma cell line harboring ALK F1174L in culture (PMID: 31852910). | 31852910 |
ALK F1174L | Advanced Solid Tumor | sensitive | ALK Inhibitor | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Repotrectinib (TPX-0005) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK F1174L in culture (PMID: 31852910). | 31852910 |
ALK F1174L | Advanced Solid Tumor | predicted - sensitive | ALK Inhibitor | Conteltinib | Preclinical - Biochemical | Actionable | In a preclinical study, Conteltinib (CT-707) inhibited ALK F1174L activity in an in vitro assay (PMID: 36424628). | 36424628 |