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|Protein Effect||loss of function - predicted|
|Gene Variant Descriptions||ALK D1270G lies within the protein kinase domain of the Alk protein (UniProt.org). D1270G results in loss of kinase activity in in vitro assays and is not transforming in culture (PMID: 33674381, PMID: 25517749), and therefore, is predicted to lead to a loss of Alk protein function.|
|Associated Drug Resistance|
|Category Variants Paths||
ALK mutant ALK inact mut ALK D1270G
|Transcript||gDNA||cDNA||Protein||Source Database||Genome Build|
|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||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...|
|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|