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Profile Name | NRAS G12V |
Gene Variant Detail | |
Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E NRAS G12V | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). | 26267534 |
BRAF V600E NRAS G12V | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and over expressing NRAS G12V in culture (PMID: 26267534). | 26267534 |
FGFR2 - PPHLN1 NRAS G12V | intrahepatic cholangiocarcinoma | predicted - resistant | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of NRAS G12V in an intrahepatic cholangiocarcinoma cell line harboring FGFR2-PPHLN1 conferred resistance to treatment with Infigratinib (BGJ398) in culture (PMID: 33709535). | 33709535 |
BRAF V600E CDKN2A loss NRAS G12V | melanoma | predicted - sensitive | Palbociclib + Ulixertinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Ibrance (palbociclib) and Ulixertinib (BVD-523) led to inhibition of tumor growth in a patient-derived xenograft (PDX) model of melanoma harboring BRAF V600E, NRAS G12V, and CDKN2A copy number loss (PMID: 34376578). | 34376578 |
BRAF V600E CDKN2A loss NRAS G12V | melanoma | predicted - resistant | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600E experienced progressive disease after a response to combination therapy with Zelboraf (vemurafenib) and Cotellic (cobimetinib), likely due to acquisition of NRAS G12V and a loss of one copy of CDKN2A (PMID: 34376578). | 34376578 |
BRAF V600E CDKN2A loss NRAS G12V | melanoma | predicted - sensitive | Palbociclib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Ibrance (palbociclib) and Mekinist (trametinib) led to inhibition of tumor growth in a patient-derived xenograft (PDX) model of melanoma harboring BRAF V600E, NRAS G12V, and CDKN2A copy number loss (PMID: 34376578). | 34376578 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT03190941 | Phase Ib/II | Cyclophosphamide anti-KRAS G12V mTCR cells Fludarabine Aldesleukin | Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients | Recruiting | USA | 0 |