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Profile Name | HRAS G13R |
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 G13R | thyroid cancer | sensitive | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an anaplastic thyroid cancer cell line harboring HRAS G13R (PMID: 21289267). | 21289267 | |
HRAS G13R | 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 G13R was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). | 32727882 | |
HRAS G13R | 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 G13R achieved a partial response (PMID: 32636318; NCT02535650). | 32636318 | |
HRAS G13R | thyroid cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
HRAS G13R | thyroid cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dasatinib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited growth and induced apoptosis in a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
HRAS G13R | thyroid cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited growth of a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
HRAS G13R | thyroid cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dasatinib + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and Koselugo (selumetinib) synergistically inhibited growth and induced apoptosis in a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
HRAS G13R | rhabdomyosarcoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Ganitumab + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) combination treatment resulted in tumor regression and increased progression-free survival in a patient-derived xenograft (PDX) model of rhabdomyosarcoma harboring HRAS G13R (PMID: 36322002). | 36322002 |
HRAS G13R | Advanced Solid Tumor | sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of HRAS G13R in an HRAS-null, NRAS-null, and KRAS knockout cell line conferred sensitivity to Zarnestra (tipifarnib) in culture, resulting in decreased cell viability (PMID: 39152269). | 39152269 | |
HRAS G13R | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Tipifarnib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with Zarnestra (tipifarnib) and Mekinist (trametinib) decreased viability of HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R compared to Zarnestra (tipifarnib) treatment alone in culture (PMID: 39152269). | 39152269 |