Molecular Profile Detail

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Profile Name NRAS G12D
Gene Variant Detail

NRAS G12D (loss of function)

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 Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF D594G NRAS G12D melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive I-BET151 Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line harboring DNMT3A R882H and NRAS G12D mutations demonstrated reduced proliferation and downregulation of a DNMT3A R882H associated gene expression profile upon I-BET151 treatment in culture, and I-BET151 treatment delayed the onset of leukemia symptoms and improved survival in xenograft mouse models derived from these cells (PMID: 31164355). 31164355
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D was sensitive to Mekinist (trametinib), demonstrating impaired disease progression and improved survival (PMID: 31164355). 31164355
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive I-BET151 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D treated with combined I-BET151 and Mekinist (trametinib) demonstrated impaired disease progression and improved survival superior to either therapy alone (PMID: 31164355). 31164355
FLT3 exon 14 ins NRAS G12D acute myeloid leukemia predicted - sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and NRAS G12D in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins NRAS G12D acute myeloid leukemia predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) failed to inhibit growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and NRAS G12D in culture (PMID: 33268594). 33268594
BRAF D594G NRAS G12D melanoma sensitive Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Mektovi (binimetinib) and Braftovi (encorafenib) resulted in a synergistic effect in melanoma cells harboring BRAF D594G and NRAS G12D, with decreased cell viability and Erk phosphorylation and increased apoptosis in culture (PMID: 35385748). 35385748
FLT3 exon 14 ins FLT3 D835X NRAS G12D NRAS G12S acute myeloid leukemia predicted - resistant Gilteritinib Case Reports/Case Series Actionable In a clinical study, a patient with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and was found to have acquired NRAS G12S and G12D (PMID: 31088841). 31088841
CBL Q367_E373delinsRLK FLT3 exon 14 ins FLT3 D835X NRAS G12D acute myeloid leukemia predicted - resistant Gilteritinib Case Reports/Case Series Actionable In a clinical study, a patient with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and was found to have acquired NRAS G12D and CBL Q367_E373delinsRLK (PMID: 31088841). 31088841
NRAS G12D NRAS L95H Advanced Solid Tumor sensitive MRTX-1133 Preclinical - Cell culture Actionable In a preclinical study, cultured cells expressing NRAS G12D and NRAS L95H were sensitive to treatment with MRTX1133, demonstrating decreased cell viability (PMID: 37339170). 37339170