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|Protein Effect||gain of function|
|Gene Variant Descriptions||ALK G1201E lies within the protein kinase domain of the Alk protein (UniProt.org). G1201E confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity and downstream Pi3k and Mapk pathway activation in culture (PMID: 21596819).|
|Associated Drug Resistance|
|Category Variants Paths||
ALK mutant ALK act mut ALK G1201E
|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||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...|