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Gene | ALK |
Variant | act mut |
Impact List | unknown |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK act mut indicates that this variant results in a gain of function in the Alk protein. However, the specific amino acid change has not been identified. |
Associated Drug Resistance | |
Category Variants Paths |
ALK mutant ALK act mut |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK act mut | neuroblastoma | sensitive | Lorlatinib | Phase I | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment was well tolerated and resulted in a modified response rate of 30% (7/23) in children and 67% (10/15) in adults with neuroblastoma harboring an ALK activating mutation, including ALK F1174C, F1174L, R1275Q, or R1275L, F1245Y, F1245L, D1276_R1279delinsE, or amplification (PMID: 37012551; NCT03107988). | 37012551 |
ALK act mut | neuroblastoma | predicted - sensitive | Navitoclax + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Mekinist (trametinib) sensitized neuroblastoma cell lines harboring ALK activating mutations to Navitoclax (ABT-263), resulting in reduced cell viability in culture (PMID: 36895472). | 36895472 |
ALK act mut | neuroblastoma | predicted - sensitive | S63845 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an ALK activating mutation to S63845 (MIK655), resulting in reduced cell viability in culture (PMID: 36895472). | 36895472 |
ALK act mut | neuroblastoma | sensitive | Cyclophosphamide + Lorlatinib + Topotecan | Phase I | Actionable | In a Phase I trial, the combination of Lorbrena (lorlatinib), Topotecan, and Cytoxan (cyclophosphamide) treatment was well tolerated and resulted in a modified response rate of 63% (5/8) in pediatric patients with neuroblastoma harboring an ALK activating mutation, including ALK F1174C, F1174L, R1275Q, or R1275L (PMID: 37012551; NCT03107988). | 37012551 |
ALK act mut | neuroblastoma | predicted - sensitive | NVL-655 | Preclinical - Cell culture | Actionable | In a preclinical study, NUV-655 inhibited proliferation of neuroblastoma cell lines harboring activating mutations in ALK in culture (Cancer Res (2022) 82 (12_Supplement): 3337). | detail... |
ALK act mut | neuroblastoma | predicted - sensitive | Trametinib + Venetoclax | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an ALK activating mutation to Venclexta (venetoclax), resulting in reduced cell viability in culture (PMID: 36895472). | 36895472 |