Molecular Profile Detail

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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