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Gene | ALK |
Variant | L1152V |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | ALK L1152V lies within the protein kinase domain of the Alk protein (UniProt.org). L1152V is associated with decreased ALK inhibitor sensitivity in the context of an ALK fusion in culture (PMID: 22034911), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2024). |
Associated Drug Resistance | |
Category Variants Paths |
ALK mutant ALK L1152V |
Transcript | NM_004304.5 |
gDNA | chr2:g.29222405G>C |
cDNA | c.3454C>G |
Protein | p.L1152V |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.4 | chr2:g.29222405G>C | c.3454C>G | p.L1152V | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29222405G>C | c.3454C>G | p.L1152V | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29222405G>C | c.3454C>G | p.L1152V | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK mutant | lung non-small cell carcinoma | no benefit | Belizatinib | Phase I | Actionable | In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). | 31217479 |
ALK mutant | lung non-small cell carcinoma | no benefit | Crizotinib + Onalespib | Phase II | Actionable | In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). | detail... |