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|Gene Variant Descriptions||HRAS act mut indicates that the variant results in activation of HRAS downstream signaling. The mechanism causing the activation can include either loss of GTP hydrolysis activity (loss of function) or increased nucleotide exchange rate (gain of function).|
|Associated Drug Resistance|
|Category Variants Paths||
HRAS mutant HRAS act mut
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|HRAS act mut||transitional cell carcinoma||predicted - sensitive||Tipifarnib||Phase II||Actionable||In a Phase II trial, Zarnestra (tipifarnib) demonstrated safety and preliminary efficacy in patients with metastatic urothelial carcinoma harboring HRAS mutations (n=14) or STK11:rs2075606, 3 of 4 patients achieved progression-free survival at 6 months harbored HRAS activating mutations, and no response was observed in HRAS wild-type patients (J Clin Oncol 38: 2020 (suppl; abstr 5086); NCT02535650).||detail...|
|HRAS act mut||salivary gland carcinoma||sensitive||Tipifarnib||Clinical Study||Actionable||In a clinical study, Zarnestra (tipifarnib) treatment resulted in an overall response rate of 8% (n=13) with one ongoing partial response with a duration of 14 months and stable disease as the best response in 58% (7/12) of evaluable patients with HRAS-mutant metastatic salivary gland carcinoma, and a median overall survival of 18 months, and a median progression-free survival of 7 months (PMID: 32557577).||32557577|
|HRAS act mut||Advanced Solid Tumor||no benefit||Selumetinib||Clinical Study - Cohort||Actionable||In a Phase II trial (MATCH), Koselugo (selumetinib) treatment resulted in a 15% (3/20) six-month progression-free survival rate, no objective responses, and did not lead to tumor regression in pediatric patients with advanced solid tumors including high grade glioma (n=8) and rhabdomyosarcoma (n=7) that harbored MAPK pathway alterations including activating HRAS, KRAS, or NRAS mutations, BRAF V600E, or inactivating NF1 mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 10008; NCT03213691, NCT03155620).||detail...|