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Profile Name | HRAS G12S |
Gene Variant Detail | |
Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor PIK3CB inhibitor PIK3CD inhibitor PIK3CG inhibitor RAS Inhibitor (Pan) |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
HRAS G12S | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS G12S was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). | 32727882 | |
HRAS G12S | renal pelvis transitional cell carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with renal pelvis transitional cell carcinoma harboring HRAS G12S achieved a partial response (PMID: 32636318; NCT02535650). | 32636318 | |
HRAS G12S | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a clinical case study, Zarnestra (tipifarnib) treatment resulted in a partial response that lasted for 8 months in a patient with ear canal squamous cell carcinoma harboring HRAS G12S (PMID: 38219706). | 38219706 | |
HRAS G12S | head and neck squamous cell carcinoma | sensitive | PIK3CA inhibitor | Alpelisib + Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with the combination of Piqray (alpelisib) and Zarnestra (tipifarnib) resulted in enhanced tumor growth inhibition compared to monotherapy in a patient-derived xenograft (PDX) model of head and neck squamous cell carcinoma harboring HRAS G12S (PMID: 38219706). | 38219706 |
HRAS G12S | lung squamous cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cisplatin + Pemetrexed Disodium + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, the addition of Mekinist (trametinib) to treament with the combination of Alimta (pemetrexed disodium) and Platinol (cisplatin) resulted in improved tumor growth inhibition compared to chemotherapy or Mekinist (trametinib) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring HRAS G12S (PMID: 39199558). | 39199558 |
HRAS G12S | lung squamous cell carcinoma | sensitive | PI3K Inhibitor (Pan) | Buparlisib + Carboplatin + Paclitaxel | Preclinical - Pdx | Actionable | In a preclinical study, the addition of Buparlisib (BKM120) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Buparlisib (BKM120) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring HRAS G12S (PMID: 39199558). | 39199558 |