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Profile Name NRAS Q61H
Gene Variant Detail

NRAS Q61H (loss of function - predicted)

Relevant Treatment Approaches MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS Q61H rhabdomyosarcoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PIK3CA inhibitor Alpelisib + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in rhabdomyosarcoma cells harboring NRAS Q61H, demonstrating cell death in culture (PMID: 29437705). 29437705
NRAS Q61H rhabdomyosarcoma not predictive Rigosertib Preclinical - Cell line xenograft Actionable In a preclinical study, Rigosertib (ON01910) inhibited cell viability and induced apoptosis and cell cycle arrest in rhabdomyosarcoma cells harboring NRAS Q61H in culture, and delayed tumor growth in cell line xenograft models, however, cells with wild-type NRAS demonstrated the same response, and mechanistically, the response was found to be due to Rigosertib (ON0190) binding to tubulin (PMID: 33158997). 33158997
NRAS Q61H rhabdomyosarcoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and viability in rhabdomyosarcoma cell lines harboring NRAS Q61H in culture, but did not inhibit ERK signaling in cell line xenograft models and led to tumor progression (PMID: 34737198). 34737198
NRAS Q61H rhabdomyosarcoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and LY3009120 combination treatment synergistically inhibited Erk phosphorylation, proliferation, and colony formation and induced cell cycle arrest and apoptosis in a rhabdomyosarcoma cell line harboring NRAS Q61H in culture (PMID: 34737198). 34737198
NRAS Q61H rhabdomyosarcoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3214996 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) and LY3214996 combination treatment synergistically inhibited growth and induced apoptosis and cell cycle arrest in a rhabdomyosarcoma cell line harboring NRAS Q61H in culture and delayed tumor growth in a xenograft model (PMID: 34737198). 34737198
NRAS Q61H rhabdomyosarcoma sensitive LY3009120 + LY3214996 Preclinical - Cell culture Actionable In a preclinical study, LY3214996 and LY3009120 combination treatment synergistically induced cell cycle arrest and apoptosis in rhabdomyosarcoma cell lines harboring NRAS Q61H in culture (PMID: 34737198). 34737198
NRAS Q61H mucosal melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited downstream signaling and decreased viability of a mucosal melanoma cell line harboring NRAS Q61H in culture (PMID: 29054983). 29054983
NRAS Q61H rhabdomyosarcoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Ganitumab + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Mekinist (trametinib) and Ganitumab (AMG-479) synergistically inhibited growth of a rhabdomyosarcoma cell line harboring NRAS Q61H in culture, but did not improve tumor suppression and survival compared to monotherapy in a cell line xenograft model (PMID: 36322002). 36322002
NRAS Q61H mucosal melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) treatment inhibited viability of patient-derived mucosal melanoma cells harboring NRAS Q61H in culture (PMID: 39001563). 39001563