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Profile Name | HRAS G12D |
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 G12D | head and neck squamous cell carcinoma | sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, Zarnestra (tipifarnib) treatment led to decreased cell viability and inhibition of clonogenic and anchorage-independent growth in head and neck squamous cell carcinoma cell lines harboring HRAS G12D in culture (PMID: 35247914). | 35247914 | |
HRAS G12D | head and neck squamous cell carcinoma | sensitive | PIK3CA inhibitor | Alpelisib + Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Piqray (alpelisib) sensitized head and neck squamous cell carcinoma cell lines harboring HRAS G12D to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and increased apoptosis in culture (PMID: 35247914). | 35247914 |
HRAS G12D | head and neck squamous cell carcinoma | sensitive | SCH772984 + Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of SCH772984 sensitized head and neck squamous cell carcinoma cell lines harboring HRAS G12D to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and increased apoptosis in culture (PMID: 35247914). | 35247914 | |
HRAS G12D | head and neck squamous cell carcinoma | sensitive | Tipifarnib + Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with Ulixertinib (BVD-523) and Zarnestra (tipifarnib) resulted in a synergistic effect, with enhanced apoptosis in a head and neck squamous cell carcinoma cell lines harboring HRAS G12D in culture (PMID: 35247914). | 35247914 | |
HRAS G12D | Advanced Solid Tumor | no benefit | MRTX-1133 | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing HRAS G12D were not sensitive to treatment with MRTX1133 (PMID: 37339170). | 37339170 |