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| Profile Name | NRAS G12C |
| 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 | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| NRAS exon3 | colon cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 3 mutations (NCCN.org). | detail... | |
| NRAS exon3 | rectum cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 3 mutations (NCCN.org). | detail... | |
| NRAS exon3 | colon cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 3 mutations (NCCN.org). | detail... | |
| NRAS exon3 | rectum cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 3 mutations (NCCN.org). | detail... | |
| NRAS act mut | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib/II trial, Kisqali (ribociclib) plus Mektovi (binimetinib) was well tolerated in NRAS-mutant melanoma patients and resulted in an overall response rate of 19.5% (8/41; all PR), disease control rate of 70.7% (29/41), median duration of response of 10.3mo, median progression-free survival of 3.7mo, and median overall survival of 11.3mo in phase II, and a response rate of 22.9% (16/70) in patients with an NRAS Q61 mutation, and 12.5% (1/8) with NRAS G12/G13 mutation (PMID: 35294522; NCT01781572). | 35294522 |
| NRAS act mut | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Clinical Study - Cohort | Actionable | In a Phase II trial (MATCH), Koselugo (selumetinib) treatment resulted in a 15% (3/20) six-month progression-free survival rate, no objective responses, and did not lead to tumor regression in pediatric patients with advanced solid tumors including high grade glioma (n=8) and rhabdomyosarcoma (n=7) that harbored MAPK pathway alterations including activating NRAS, HRAS, or KRAS mutations, BRAF V600E, or inactivating NF1 mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 10008; NCT03213691, NCT03155620). | detail... |
| NRAS act mut | lung non-small cell carcinoma | predicted - resistant | Osimertinib | Case Reports/Case Series | Actionable | In a retrospective analysis, activating NRAS mutations were identified in 1 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). | 31839416 | |
| CDKN2A mut NRAS act mut | acute lymphoblastic leukemia | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human acute lymphoblastic leukemia cells harboring NRAS and CDKN2A mutations were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| FGFR3 rearrange NRAS act mut | multiple myeloma | no benefit | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a multiple myeloma cell line harboring an FGFR3 rearrangement and an NRAS activating mutation was not sensitive to treatment with Futibatinib (TAS-120) in culture (PMID: 32973082). | 32973082 | |
| NRAS over exp | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mektovi (binimetinib) treatment in melanoma cell lines with NRAS overexpression, but without NRAS or BRAF mutations, resulted in reduced downstream signaling and proliferation in cultured cells (PMID: 29245078). | 29245078 |
| FGFR1 amp NRAS over exp | lung non-small cell carcinoma | decreased response | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, overexpression of Nras in FGFR1-amplified non-small cell lung carcinoma cells resulted in decreased response to Truseltiq (infigratinib) in culture (PMID: 28630215). | 28630215 | |
| FGFR1 amp NRAS over exp | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Infigratinib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) and Mekinist (trametinib) combination treatment inhibited Erk signaling, resulting in growth inhibition in FGFR1-amplified non-small cell lung carcinoma cells overexpressing Nras in culture (PMID: 28630215). | 28630215 |
| BRAF V600E NRAS over exp | colorectal cancer | resistant | Cetuximab + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, overexpression of wild-type NRAS in colorectal cancer cell lines harboring BRAF V600E induced Ras activation and Braf/Craf dimerization, conferred resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture and in cell line xenograft models (PMID: 28951457). | 28951457 | |
| BRAF V600E NRAS over exp | colorectal cancer | sensitive | BGB659 + Cetuximab | Preclinical - Cell culture | Actionable | In a preclinical study, BGB659 and Erbitux (cetuximab) combination treatment demonstrated enhanced inhibition of Erk phosphorylation and growth in BRAF V600E colorectal cancer cell lines overexpressing Nras in culture (PMID: 28951457). | 28951457 | |
| NRAS G13V | adult T-cell leukemia/lymphoma | sensitive | RAS Inhibitor (Pan) | 3144 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, 3144 inhibited growth of patient-derived T-cell acute lymphocytic leukemia cells harboring NRAS G13V in culture, and reduced tumor burden in xenograft models (PMID: 28235199). | 28235199 |
| NRAS K117X | colorectal cancer | resistant | Panitumumab | FDA contraindicated | Actionable | Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 4, codon 117 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS K117X | colorectal cancer | resistant | Cetuximab | FDA contraindicated | Actionable | Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 4, codon 117 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS Q61K | melanoma | predicted - sensitive | Belvarafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Belvarafenib (HM95573) treatment led to inhibition of tumor growth in a melanoma cell line xenograft model harboring NRAS Q61K (PMID: 33953400). | 33953400 | |
| NRAS Q61K | uveal melanoma | no benefit | YM-254890 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed mouse melanocytes expressing NRAS Q61K were insensitive to treatment with YM-254890 (PMID: 33229459). | 33229459 | |
| NRAS Q61K | neuroblastoma | sensitive | SHP099 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of SHP099 and Zelboraf (vemurafenib) in neuroblastoma cell lines either expressing or harboring NRAS Q61K resulted in increased sensitivity compared to Zelboraf (vemurafenib) treatment alone in culture, demonstrating a greater decrease in cell viability (PMID: 32586982). | 32586982 | |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Everolimus + Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). | 23629727 |
| NRAS Q61K | melanoma | sensitive | ASTX029 | Preclinical - Pdx | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of melanoma cell lines harboring NRAS Q61K in culture, and inhibited tumor growth in a patient-derived xenograft (PDX) model of melanoma harboring NRAS Q61K (PMID: 34330842). | 34330842 | |
| NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mektovi (binimetinib) and RAF709 resulted in inhibition of cell growth in a MEK inhibitor-resistant melanoma cell line harboring NRAS Q61K (PMID: 33318037). | 33318037 |
| NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). | 23414587 |
| NRAS Q61K | lung non-small cell carcinoma | predicted - resistant | BI-3406 | Preclinical - Cell culture | Actionable | In a preclinical study, BI-3406 treatment failed to inhibit growth of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 32816843). | 32816843 | |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lifirafenib (BGB-283) and PD-0325901 synergistically inhibited proliferation of a non-small cell lung cancer cell line harboring NRAS Q61K in culture, and demonstrated improved efficacy over either agent alone (PMID: 32336014). | 32336014 |
| NRAS Q61K | melanoma | decreased response | BGB-283 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Lifirafenib (BGB-283) and Zelboraf (vemurafenib) in Mekinist (trametinib)-resistant melanoma cells harboring NRAS Q61K in culture resulted in a decreased response compared to the combination treatment with Lifirafenib (BGB-283) and Mekinist (trametinib), demonstrating reduced inhibition of cell growth (PMID: 33318037). | 33318037 | |
| NRAS Q61K | neuroblastoma | predicted - sensitive | Ulixertinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, neuroblastoma cell lines either harboring or expressing NRAS Q61K demonstrated moderate growth inhibition in culture when treated with Ulixertinib (BVD-523) (PMID: 32586982). | 32586982 | |
| NRAS Q61K | melanoma | predicted - sensitive | UCM-1336 | Preclinical - Cell culture | Actionable | In a preclinical study, UCM-1336 treatment inhibited growth of melanoma cells harboring NRAS Q61K in culture (PMID: 31181882). | 31181882 | |
| NRAS Q61K | neuroblastoma | no benefit | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, neuroblastoma cells with NRAS Q61K showed minimal response to treatment with Zelboraf (vemurafenib) in culture (PMID: 32586982). | 32586982 | |
| NRAS Q61K | lung carcinoma | sensitive | Abemaciclib + LY3214996 | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with LY3214996 and Verzenio (abemaciclib) led to additive effects on tumor growth inhibition in a patient-derived xenograft (PDX) model of lung carcinoma harboring NRAS Q61K (PMID: 33536188). | 33536188 | |
| NRAS Q61K | neuroblastoma | predicted - resistant | SHP099 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, neuroblastoma cell lines either harboring or expressing NRAS Q61K demonstrated resistance to treatment with SHP099, with increased cell viability and proliferation compared to wild-type Nras in culture, and moderate growth inhibition in cell line xenograft models compared when compared to combination therapies (PMID: 32586982). | 32586982 | |
| NRAS Q61K | lung cancer | sensitive | RAF709 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RAF709 inhibited Erk signaling and proliferation of lung cancer cells harboring NRAS Q61K in culture, and resulted in tumor regression in cell line xenograft models (PMID: 29343524). | 29343524 | |
| NRAS Q61K | acute myeloid leukemia | predicted - sensitive | UCM-1336 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, UCM-1336 treatment inhibited growth of acute myeloid leukemia cells harboring NRAS Q61K in culture, and reduced bone marrow tumor burden and significantly prolonged survival (HR=6.211; p=0.0274) in cell line xenograft models (PMID: 31181882). | 31181882 | |
| NRAS Q61K | neuroblastoma | sensitive | SHP099 + Ulixertinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination treatment of SHP099 and Ulixertinib (BVD-523) resulted in a synergistic effect in neuroblastoma cell line xenograft models harboring NRAS Q61K, demonstrating a greater delay in tumor growth when compared to either agent alone (PMID: 32586982). | 32586982 | |
| NRAS Q61K | melanoma | no benefit | BGB-283 + Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Ulixertinib (BVD-523) to Lifirafenib (BGB-283) treatment did not lead to inhibition of cell growth when compared to the combination treatment of Lifirafenib (BGB-283) and Mekinist (trametinib) in MEK inhibitor resistant melanoma cells harboring NRAS Q61K in culture (PMID: 33318037). | 33318037 | |
| NRAS Q61K | neuroblastoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, neuroblastoma cell lines either harboring or expressing NRAS Q61K demonstrated moderate growth inhibition in culture and in cell line xenograft models when treated with Mekinist (trametinib) (PMID: 32586982). | 32586982 |
| NRAS Q61K | neuroblastoma | sensitive | ERAS-007 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited tumor growth in a neuroblastoma cell line xenograft model harboring NRAS Q61K (PMID: 34337566). | 34337566 | |
| NRAS Q61K | lung non-small cell carcinoma | decreased response | PI3K Inhibitor (Pan) | Gedatolisib | Preclinical | Actionable | In a preclinical study, human non-small cell lung cancer cells harboring NRAS Q61K had a decreased response to Gedatolisib (PKI-587) in culture (PMID: 21325073, PMID: 12068308). | 21325073 12068308 |
| NRAS Q61K | neuroblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | SHP099 + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination treatment of SHP099 and Mekinist (trametinib) resulted in a synergistic effect in neuroblastoma cell lines either harboring or expressing NRAS Q61K, demonstrating greater cell growth inhibition compared to either agent alone in culture and delayed tumor growth, increased apoptotic activity, and improved survival in cell line xenograft models (PMID: 32586982). | 32586982 |
| NRAS Q61K | melanoma | decreased response | BGB-283 + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Lifirafenib (BGB-283) and SCH772984 in Mekinist (trametinib)-resistant melanoma cells harboring NRAS Q61K in culture resulted in a decreased response compared to the combination treatment with Lifirafenib (BGB-283) and Mekinist (trametinib), demonstrating reduced inhibition of cell growth (PMID: 33318037). | 33318037 | |
| NRAS Q61K | lung carcinoma | sensitive | LY3214996 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, patient-derived lung carcinoma cells harboring NRAS Q61K were sensitive to LY3214996 treatment in culture, and LY3214996 treatment led to reduction of tumor growth in a patient-derived xenograft (PDX) model (PMID: 33536188). | 33536188 | |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lifirafenib (BGB-283) and Pimasertib (MSC1936369B) synergistically inhibited proliferation of a non-small cell lung cancer cell line harboring NRAS Q61K in culture, and demonstrated improved efficacy over either agent alone (PMID: 32336014). | 32336014 |
| NRAS Q61K | neuroblastoma | 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 neuroblastoma cells harboring NRAS Q61K 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 Q61K | melanoma | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a cell line xenograft model of melanoma harboring NRAS Q61K demonstrated resistance to Zelboraf (vemurafenib) treatment (PMID: 30559419). | 30559419 | |
| NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring NRAS Q61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 | |
| NRAS Q61K | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring NRAS Q61K in culture (PMID: 26343583). | 26343583 | |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). | 23629727 |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). | 23629727 |
| NRAS Q61K | melanoma | predicted - sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, RAF709 inhibited Erk signaling in melanoma cells harboring NRAS Q61K in culture (PMID: 29343524). | 29343524 | |
| NRAS Q61K | melanoma | no benefit | BGB-283 + MK-8353 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of MK-8353 to Lifirafenib (BGB-283) treatment did not lead to inhibition of cell growth when compared to the combination treatment of Lifirafenib (BGB-283) and Mekinist (trametinib) in MEK inhibitor resistant melanoma cells harboring NRAS Q61K in culture (PMID: 33318037). | 33318037 | |
| NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cell lines harboring NRAS Q61K in culture (PMID: 26343583). | 26343583 |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). | 23629727 |
| NRAS Q61K | melanoma | resistant | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX8394 treatment did not inhibit Erk signaling or reduce tumor growth in a Zelboraf (vemurafenib)-resistant cell line xenograft model of melanoma harboring NRAS Q61K (PMID: 30559419). | 30559419 | |
| NRAS Q61K | melanoma | sensitive | Chelidonine | Preclinical - Cell culture | Actionable | In a preclinical study, Chelidonine treatment inhibited activation of Nras and downstream signaling pathways, reduced proliferation and colony formation, and induced apoptosis in melanoma cells harboring NRAS Q61K in culture (PMID: 32156748). | 32156748 | |
| NRAS Q61K | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Case Reports/Case Series | Actionable | In a Phase II trial (MATCH), Mektovi (binimetinib) treatment resulted in stable disease in two patient with colorectal cancer harboring NRAS Q61K, whom remained on treatment for 12 and 17 months until disease progression (PMID: 33637626; NCT02465060). | 33637626 |
| BRAF V600E NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing NRAS Q61K were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS Q61K | melanoma | sensitive | XL888 | Preclinical | Actionable | In a preclinical study, treatment with XL888 resulted in increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant melanoma cells harboring BRAF V600E along with NRAS Q61K in cell culture (PMID: 22351686). | 22351686 | |
| BRAF V600E NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, a NRAS Q61K mutation conferred resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). | 21107323 | |
| BRAF V600E NRAS Q61K | melanoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600E experienced progressive disease after response to treatment Zelboraf (vemurafenib), and was found to have acquired NRAS Q61K (PMID: 34376578). | 34376578 | |
| BRAF V600E NRAS Q61K | colorectal cancer | predicted - resistant | Panitumumab + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 40 weeks to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, NRAS Q61K was identified as an acquired mutation at the time of progression (PMID: 28951457). | 28951457 | |
| BRAF V600E NRAS Q61K | melanoma | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation and inhibited growth of a melanoma cell line harboring BRAF V600E and expressing NRAS Q61K in culture (PMID: 34330842). | 34330842 | |
| BRAF V600E NRAS Q61K | lung adenocarcinoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). | 29631033 |
| CDKN2A loss NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). | 22983396 |
| CDKN2A loss NRAS Q61K | melanoma | sensitive | SBI-0640756 | Preclinical | Actionable | In a preclinical study, SBI-0640726 delayed tumor growth of melanomas in mice with a genetic background of NRAS Q61K and CDKN2A loss (PMID: 26603897). | 26603897 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | PI3K Inhibitor (Pan) | GSK2126458 | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | conflicting | PI3K Inhibitor (Pan) | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | decreased response | PI3K Inhibitor (Pan) | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | PI3K Inhibitor (Pan) | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600K NRAS Q61K | melanoma | sensitive | PI3K Inhibitor (Pan) | GSK2126458 | Preclinical | Actionable | In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS Q61K NRAS A146T | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
| BRAF G469R NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cells harboring BRAF G469R and NRAS G61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 | |
| BRAF G469R NRAS Q61K | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). | 26343583 | |
| BRAF G469R NRAS Q61K | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). | 26343583 |
| BRAF V600X BRAF amp NRAS Q61K | melanoma | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, BRAF amplification and NRAS Q61K, during treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 | |
| BRAF wild-type NRAS Q61K | melanoma | resistant | GDC0879 | Preclinical - Pdx | Actionable | In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type melanoma cells harboring NRAS Q61K in patient-derived xenograft models (PMID: 19276360). | 19276360 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). | 27523909 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). | 27523909 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61L demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). | 27523909 | |
| BRAF G466V NRAS Q61K | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). | 28783719 |
| BRAF G469V NRAS Q61K | melanoma | no benefit | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 | |
| BRAF G469V NRAS Q61K | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 |
| BRAF G469V NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Encorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 |
| BRAF G469V NRAS Q61K | melanoma | sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 inhibited growth of a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 | |
| BRAF G469V NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 |
| ATM T1200Lfs*7 NRAS Q61K TP53 R213* | sarcoma | predicted - resistant | Olaparib | Case Reports/Case Series | Actionable | In a clinical case study, Lynparza (olaparib) treatment resulted in rapid disease progression in a patient with high-grade sarcoma harboring ATM T1200Lfs*7, NRAS Q61K, and TP53 R213* (PMID: 29304353). | 29304353 | |
| NRAS Q61K NRAS mut | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| NRAS Q61K NRAS mut | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture (PMID: 30819666). | 30819666 |
| NRAS Q61K NRAS mut | melanoma | decreased response | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated a decreased response to treatment with Ibrance (palbociclib) in culture compared to control (PMID: 30819666). | 30819666 | |
| BRAF D287H NRAS Q61K | melanoma | predicted - sensitive | LXH 254 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line harboring BRAF D287H and NRAS Q61K was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model of melanoma (PMID: 33355204). | 33355204 | |
| BRAF loss NRAS Q61K | melanoma | decreased response | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, CRISPR-Cas9 mediated knockout of BRAF in a melanoma cell line harboring NRAS Q61K led to decreased sensitivity to LXH254 treatment compared to parental cells harboring BRAF D287H and NRAS Q61K in culture (PMID: 33355204). | 33355204 | |
| BRAF L597Q FGFR2 H167_N173del FGFR2 N550K FGFR2 L618F NRAS Q61K | intrahepatic cholangiocarcinoma | predicted - resistant | LY3214996 | Case Reports/Case Series | Actionable | In a clinical case study, acquired NRAS Q61K and FGFR2 N550K mutations were identified following progression on LY3214996 in an intrahepatic cholangiocarcinoma patient harboring BRAF L597Q, FGFR2 H167_N173del, and FGFR2 L618F (PMID: 33926920). | 33926920 | |
| BRAF V600E CDKN2A loss NRAS Q61K | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600E and NRAS Q61K experienced progressive disease after a response to combination therapy with Zelboraf (vemurafenib) and Cotellic (cobimetinib), land was found to have acquired loss of CDKN2A (PMID: 34376578). | 34376578 |
| BRAF V600D NRAS dec exp | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600D and knockdown of NRAS demonstrated a decreased response to Mektovi (binimetinib) relative to cells without NRAS knockdown in culture (PMID: 29245078). | 29245078 |
| NRAS K135N | colorectal cancer | predicted - sensitive | Cetuximab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a cell line xenograft model of colorectal cancer expressing KRAS K135N demonstrated similar sensitivity to Erbitux (cetuximab) treatment compared to a KRAS wild-type model (PMID: 34117033). | 34117033 | |
| BRAF G596V NRAS G13R | colorectal cancer | sensitive | Cetuximab + LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in a patient-derived xenograft model of colorectal cancer harboring BRAF G596V and NRAS G13R (PMID: 28611205). | 28611205 | |
| BRAF V600E NRAS G13R | colorectal cancer | predicted - resistant | PIK3CA inhibitor | Alpelisib + Cetuximab + Encorafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 24 weeks to Alpelisib (BYL719), Erbitux (cetuximab), and Braftovi (encorafenib) combination treatment, NRAS G13R was identified as an acquired mutation in liver metastasis at the time of progression (PMID: 28951457). | 28951457 |
| BRAF V600E NRAS G13R | colorectal cancer | predicted - sensitive | BGB659 + Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, BGB659 and Erbitux (cetuximab) combination treatment resulted in sustained inhibition of Mek and Erk phosphorylation, lead to tumor regression in patient-derived xenograft models of colorectal cancer harboring BRAF V600E and NRAS G13R (PMID: 28951457). | 28951457 | |
| NRAS G12X | colorectal cancer | resistant | Cetuximab | FDA contraindicated | Actionable | Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 2, codon 12 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS G12X | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial (MATCH), Mektovi (binimetinib) treatment resulted in an objective response rate of 2.1% (1/47) that was deemed nonpromising in patients with advanced solid tumors harboring NRAS mutations at codon 12 (n=17), 13 (n=8), or 61 (n=22), with a 6-month progression-free survival (PFS) of 29.2%, a median PFS of 3.5 months, and a median overall survival of 10.5 months (PMID: 33637626; NCT02465060). | 33637626 |
| NRAS G12X | colorectal cancer | resistant | Panitumumab | FDA contraindicated | Actionable | Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 2, codon 12 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS G12X | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | NRAS G12X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... | |
| NRAS exon2 | rectum cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 2 mutations (NCCN.org). | detail... | |
| NRAS exon2 | rectum cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 2 mutations (NCCN.org). | detail... | |
| NRAS exon2 | colon cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org). | detail... | |
| NRAS exon2 | colon cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org). | detail... | |
| NRAS amp | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) treatment resulted in reduced tumor growth and proliferation in two patient-derived xenograft (PDX) melanoma models with NRAS copy number gain and without BRAF or NRAS mutations (PMID: 29245078). | 29245078 |
| FGFR1 amp NRAS amp | lung non-small cell carcinoma | resistant | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, amplification of NRAS was identified in a non-small cell lung cancer cell line harboring FGFR1 amplification that acquired resistance to Truseltiq (infigratinib) in culture (PMID: 28630215). | 28630215 | |
| FGFR1 amp NRAS amp | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Infigratinib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) and Mekinist (trametinib) combination treatment inhibited Erk signaling, resulting in growth inhibition in non-small cell lung carcinoma cells harboring both FGFR1 and NRAS amplification in culture (PMID: 28630215). | 28630215 |
| FGFR1 amp NRAS amp | lung non-small cell carcinoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells harboring both FGFR1 and NRAS amplification were resistant to Mekinist (trametinib) in culture (PMID: 28630215). | 28630215 |
| BRAF V600E NRAS amp | colorectal cancer | predicted - resistant | Panitumumab + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after achieving stable disease for 16 weeks with Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, NRAS amplification was identified as an acquired alteration at the time of progression (PMID: 28951457). | 28951457 | |
| NRAS Q61R | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Chloroquine + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Mekinist (trametinib) and Chloroquine resulted in tumor regression in a melanoma patient-derived xenograft (PDX) model harboring NRAS Q61R (PMID: 30833748). | 30833748 |
| NRAS Q61R | melanoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of melanoma cell lines harboring NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34330842). | 34330842 | |
| NRAS Q61R | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). | 23414587 |
| NRAS Q61R | melanoma | resistant | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring NRAS Q61R demonstrated resistance to PLX8394 treatment in culture (PMID: 30559419). | 30559419 | |
| NRAS Q61R | melanoma | predicted - sensitive | BGB659 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB659 treatment inhibited Erk activation and reduced proliferation of melanoma cells harboring NRAS Q61R and wild-type RAF in culture (PMID: 30559419). | 30559419 | |
| NRAS Q61R | melanoma | sensitive | Chelidonine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chelidonine treatment inhibited activation of Nras and downstream signaling pathways, reduced proliferation and colony formation, and induced apoptosis in melanoma cells harboring NRAS Q61R in culture, and inhibited tumor growth and increased survival in a cell line xenograft model (PMID: 32156748). | 32156748 | |
| NRAS Q61R | ameloblastoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Case Reports/Case Series | Actionable | In a Phase II trial (MATCH), Mektovi (binimetinib) treatment resulted in a partial response in a patient with metastatic malignant ameloblastoma harboring NRAS Q61R, and the patient stayed on treatment for 26 months (PMID: 33637626; NCT02465060). | 33637626 |
| NRAS Q61R | melanoma | predicted - sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 treatment inhibited Erk activation and reduced proliferation of melanoma cells harboring NRAS Q61R and wild-type RAF in culture, but at a higher concentration than was required to inhibit melanoma cells harboring BRAF V600E (PMID: 30559419). | 30559419 | |
| NRAS Q61R | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) resulted in durable tumor regression compared to stabilized tumor growth when treated with either agent alone in patient-derived xenograft (PDX) models of melanoma harboring NRAS Q61R (PMID: 33318037). | 33318037 |
| NRAS Q61R | urinary bladder cancer | sensitive | RAF265 | Preclinical - Cell culture | Actionable | In a preclinical study, RAF265 treatment decreased viability of a bladder cancer cell line harboring NRAS Q61R in culture (PMID: 34554931). | 34554931 | |
| NRAS Q61R | melanoma | predicted - sensitive | Belvarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Belvarafenib (HM95573) treatment in a melanoma patient harboring NRAS Q61R led to a tumor reduction of 84% after 24 weeks of treatment and a confirmed partial response at 12 weeks, and response to treatment was maintained for 40 weeks (PMID: 33953400; NCT03118817). | 33953400 | |
| NRAS Q61R | urinary bladder cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | LXH 254 + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LXH 254 and Mekinist (trametinib) combination treatment decreased tumor volume and weight compared to vehicle in a cell line xenograft model of bladder cancer harboring NRAS Q61R (PMID: 34554931). | 34554931 |
| NRAS Q61R | urinary bladder cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RAF265 + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RAF265 and Mekinist (trametinib) combination treatment decreased Erk1/2 phosphorylation in cultured cells and decreased tumor volume and weight of a cell line xenograft model harboring NRAS Q61R (PMID: 34554931). | 34554931 |
| NRAS Q61R | melanoma | sensitive | ERAS-007 | Preclinical - Cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a melanoma cell line harboring NRAS Q61R in culture (PMID: 34337566). | 34337566 | |
| NRAS Q61R | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Case Reports/Case Series | Actionable | In a Phase II trial (MATCH), Mektovi (binimetinib) treatment resulted in an unconfirmed partial response in a patient with colorectal cancer harboring NRAS Q61R, with a 48.2% tumor reduction at cycle 4, but the disease progressed at cycle 7 (PMID: 33637626; NCT02465060). | 33637626 |
| NRAS Q61R | thyroid gland cancer | sensitive | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an anaplastic thyroid cancer cell line harboring NRAS Q61R (PMID: 21289267). | 21289267 | |
| NRAS Q61R | melanoma | predicted - sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 treatment inhibited Erk activation and reduced proliferation of melanoma cells harboring NRAS Q61R and wild-type RAF in culture (PMID: 30559419). | 30559419 | |
| NRAS Q61R | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mektovi (binimetinib) and RAF709 resulted in inhibition of cell growth in a MEK inhibitor-resistant melanoma cell line harboring NRAS Q61R (PMID: 33318037). | 33318037 |
| NRAS Q61R | acute biphenotypic leukemia | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a clinical study, Mekinist (trametinib) treatment was well tolerated and led to an initial decrease of peripheral blasts in a pediatric patient with mixed phenotype acute leukemia harboring NRAS Q61R who had previously undergone a stem cell transplant, but patient experienced progressive disease after 2 months, and died soon after (PMID: 33563661; NCT02670525). | 33563661 |
| NRAS Q61R | urinary bladder cancer | sensitive | LXH 254 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LXH 254 treatment decreased Mek signaling, colony formation and viability, and increased apoptosis in a bladder cancer cell line harboring NRAS Q61R in culture and decreased tumor weight and volume in a cell line xenograft model (PMID: 34554931). | 34554931 | |
| NRAS Q61R | Advanced Solid Tumor | sensitive | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NRAS Q61R were sensitive to treatment with Belvarafenib (HM95573) in culture, demonstrating decreased cell viability (PMID: 33953400). | 33953400 | |
| NRAS Q61R | melanoma | decreased response | BGB-283 + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Lifirafenib (BGB-283) and SCH772984 in Mekinist (trametinib)-resistant melanoma cells harboring NRAS Q61R in culture resulted in a decreased response compared to the combination treatment with Lifirafenib (BGB-283) and Mekinist (trametinib), demonstrating reduced inhibition of cell growth (PMID: 33318037). | 33318037 | |
| NRAS Q61R | urinary bladder cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Mekinist (trametinib) treatment decreased tumor weight of a cell line xenograft model of bladder cancer harboring NRAS Q61R (PMID: 34554931). | 34554931 |
| BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R | melanoma | predicted - resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistance-associated mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 | |
| KIT D816V NRAS Q61R | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pembrolizumab + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring KIT D816V and NRAS Q61R demonstrated progressive disease when treated with a combination of Mekinist (trametinib) and Keytruda (pembrolizumab) (PMID: 28514312). | 28514312 |
| ATM mut NRAS Q61R | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring an ATM mutation and NRAS Q61R demonstrated a partial response and 16 month progression free survival when treated with Binimetinib (MEK162) (PMID: 28514312). | 28514312 |
| BRAF V600E MAP2K1 Q56P NRAS Q61R | melanoma | sensitive | AZD0364 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD0364 (ATG-017) decreased phosphorylation of Erk target genes and increased expression of apoptosis markers in melanoma cells harboring BRAF V600E, MAP2K1 Q56P, and NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 33273059). | 33273059 | |
| NRAS Q61L | acute myeloid leukemia | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 treatment induced apoptosis and inhibited proliferation of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 28923853). | 28923853 |
| NRAS Q61L | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cells harboring NRAS Q61L were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 | |
| NRAS Q61L | melanoma | sensitive | CCT241161 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CCT241161 inhibited MEK and ERK activation and growth of a melanoma cell line harboring NRAS Q61L in culture, and inhibited tumor growth in a NRAS Q61L-mutant melanoma cell line xenograft model (PMID: 25500121, PMID: 23431193). | 25500121 23431193 | |
| NRAS Q61L | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring NRAS Q61L in culture (PMID: 26343583). | 26343583 |
| NRAS Q61L | melanoma | resistant | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 did not inhibit growth of melanoma cells harboring NRAS Q61L in culture or in cell line xenograft models (PMID: 25500121, PMID: 23431193). | 25500121 23431193 | |
| NRAS Q61L | melanoma | sensitive | Chelidonine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chelidonine treatment inhibited activation of Nras and downstream signaling pathways, reduced proliferation and colony formation, and induced apoptosis in melanoma cells harboring NRAS Q61L in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 32156748). | 32156748 | |
| NRAS Q61L | acute myeloid leukemia | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, addition of Nexavar (sorafenib) to PD-0325901 treatment did not demonstrate increased sensitivity compared to PD-0325901 alone in an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 28923853). | 28923853 |
| NRAS Q61L | acute myeloid leukemia | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring NRAS Q61L were sensitive to treatment with ASTX029 in culture (PMID: 34330842). | 34330842 | |
| NRAS Q61L | melanoma | predicted - sensitive | LY3214996 | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring NRAS Q61L was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895). | 31744895 | |
| NRAS Q61L | melanoma | no benefit | BGB-283 + Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Ulixertinib (BVD-523) to Lifirafenib (BGB-283) treatment did not lead to inhibition of cell growth when compared to the combination treatment of Lifirafenib (BGB-283) and Mekinist (trametinib) in MEK inhibitor resistant melanoma cells harboring NRAS Q61L in culture (PMID: 33318037). | 33318037 | |
| NRAS Q61L | 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 Q61L in culture (PMID: 34737198). | 34737198 |
| NRAS Q61L | 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 Q61L in culture (PMID: 34737198). | 34737198 | |
| NRAS Q61L | rhabdomyosarcoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | LY3214996 + Trametinib | Preclinical - Cell culture | 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 Q61L in culture (PMID: 34737198). | 34737198 |
| NRAS Q61L | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mektovi (binimetinib) and RAF709 resulted in inhibition of cell growth in a MEK inhibitor-resistant melanoma cell line harboring NRAS Q61L (PMID: 33318037). | 33318037 |
| NRAS Q61L | melanoma | decreased response | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 modestly inhibited soft agar growth of human melanoma cancer cells harboring NRAS Q61L in culture (PMID: 26343583). | 26343583 | |
| NRAS Q61L | melanoma | sensitive | CCT196969 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CCT196969 inhibited MEK and ERK activation and growth of a melanoma cell line harboring NRAS Q61L in culture, and inhibited tumor growth in a NRAS Q61L-mutant melanoma cell line xenograft model (PMID: 25500121, PMID: 23431193). | 25500121 23431193 | |
| NRAS Q61L | melanoma | sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, RAF709 inhibited Erk signaling and proliferation of melanoma cells harboring NRAS Q61L in culture (PMID: 29343524). | 29343524 | |
| NRAS Q61L | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Belvarafenib + Cobimetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the addition of Cotellic (cobimetinib) to treatment with Belvarafenib (HM95573) in melanoma cell lines harboring NRAS Q61L resulted in greater inhibition of cell proliferation in culture compared to single agent alone, and led to decreased tumor volume, with increased efficacy and response durability in a cell line xenograft model (PMID: 33953400). | 33953400 |
| NRAS Q61L | melanoma | decreased response | BGB-283 + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Lifirafenib (BGB-283) and SCH772984 in Mekinist (trametinib)-resistant melanoma cells harboring NRAS Q61L in culture resulted in a decreased response compared to the combination treatment with Lifirafenib (BGB-283) and Mekinist (trametinib), demonstrating reduced inhibition of cell growth (PMID: 33318037). | 33318037 | |
| NRAS Q61L | melanoma | no benefit | BGB-283 + MK-8353 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of MK-8353 to Lifirafenib (BGB-283) treatment did not lead to inhibition of cell growth when compared to the combination treatment of Lifirafenib (BGB-283) and Mekinist (trametinib) in MEK inhibitor resistant melanoma cells harboring NRAS Q61L in culture (PMID: 33318037). | 33318037 | |
| NRAS Q61L | melanoma | decreased response | BGB-283 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Lifirafenib (BGB-283) and Zelboraf (vemurafenib) in Mekinist (trametinib)-resistant melanoma cells harboring NRAS Q61L in culture resulted in a decreased response compared to the combination treatment with Lifirafenib (BGB-283) and Mekinist (trametinib), demonstrating reduced inhibition of cell growth (PMID: 33318037). | 33318037 | |
| NRAS Q61L | liver cancer | sensitive | ERAS-007 | Preclinical - Cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a liver cancer cell line harboring NRAS Q61L in culture (PMID: 34337566). | 34337566 | |
| NRAS Q61L | urinary bladder cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RAF265 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, RAF265 and Mekinist (trametinib) combination treatment inhibited colony formation compared to RAF265 alone in cultured cells harboring NRAS Q61L (PMID: 34554931). | 34554931 |
| NRAS Q61L | urinary bladder cancer | sensitive | RAF265 | Preclinical - Cell culture | Actionable | In a preclinical study, RAF265 treatment decreased colony formation of a bladder cancer cell line harboring NRAS Q61L in culture (PMID: 34554931). | 34554931 | |
| NRAS Q61L | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). | 23414587 |
| NRAS Q61L NRAS mut | melanoma | decreased response | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated a decreased response to treatment with Ibrance (palbociclib) in culture when compared to control (PMID: 30819666). | 30819666 | |
| NRAS Q61L NRAS mut | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| NRAS Q61L NRAS mut | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated resistance to the combination treatment with Mekinist (trametinib) and Ibrance (palbociclib) in culture (PMID: 30819666). | 30819666 |
| BRAF G534D NRAS Q61L | melanoma | resistant | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of BRAF G534D in a melanoma cell line harboring NRAS Q61L conferred resistance to treatment with Belvarafenib (HM95573) in culture (PMID: 33953400). | 33953400 | |
| BRAF V600E NRAS Q61L | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing NRAS Q61L demonstrated resistance to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| 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 | 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 | 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 | 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 | 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 | 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 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | no benefit | PI3K Inhibitor (Pan) | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | decreased response | PI3K Inhibitor (Pan) | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | sensitive | PI3K Inhibitor (Pan) | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | decreased response | PI3K Inhibitor (Pan) | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were >10-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| NRAS G12V | colorectal cancer | resistant | Cetuximab | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring NRAS G12V demonstrated resistance to Erbitux (cetuximab) in culture (PMID: 28179366). | 28179366 | |
| NRAS G12V | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring NRAS G12V in culture (PMID: 28179366). | 28179366 |
| 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 | |
| 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 | |
| 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 | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 |
| BRAF V600E CDKN2A loss NRAS G12V | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 + 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 | |
| NRAS Q61X | colorectal cancer | resistant | Cetuximab | FDA contraindicated | Actionable | Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 3, codon 61 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS Q61X | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | NRAS Q61X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... | |
| NRAS Q61X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib/II trial, Kisqali (ribociclib) plus Mektovi (binimetinib) was well tolerated in NRAS-mutant melanoma patients and resulted in an overall response rate (ORR) of 19.5% (8/41; all PR), disease control rate of 70.7% (29/41), median duration of response of 10.3 months, median progression-free survival of 3.7 months, and median overall survival (OS) of 11.3 months in the phase II cohort, and a response rate of 22.9% (16/70) in patients with an NRAS Q61 mutation overall (PMID: 35294522; NCT01781572). | 35294522 |
| NRAS Q61X | colorectal cancer | resistant | Panitumumab | FDA contraindicated | Actionable | Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 3, codon 61 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS Q61X | Advanced Solid Tumor | unknown | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial (MATCH), Mektovi (binimetinib) therapy led to a nonpromising objective response rate of 2.1% (1/47) in patients (pts) with advanced solid tumors harboring NRAS G12/13 or Q61 mutations, Q61-mutant pts achieved longer overall survival (13.1 vs 5.5 mo, p=0.04) and progression-free survival (5.8 vs 1.8 mo, p=0.006) compared to G12/13-mutant pts examining all tumor types, but not when colorectal caner was excluded (HR 0.84, p=0.70; HR 0.67, p=0.4, respectively) (PMID: 33637626; NCT02465060). | 33637626 |
| NRAS Q61X | colorectal cancer | unknown | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial (MATCH), Mektovi (binimetinib) treatment did not demonstrate promising efficacy in patients with advanced solid tumors harboring NRAS mutations at codon 12 (n=17), 13 (n=8), or 61 (n=22), however, colorectal cancer patients harboring NRAS Q61 mutations (n=8) achieved longer overall survival (HR 0.34, p=0.03) and progression-free survival (HR 0.23, p=0.007) compared to those harboring mutations at G12 or G13 (n=16) (PMID: 33637626; NCT02465060). | 33637626 |
| NRAS G12D | colorectal cancer | predicted - sensitive | RAS Inhibitor (Pan) | GI-4000 | Phase I | Actionable | In a Phase I trial, GI-4000 was well tolerated, induced immune response in 61.3% (19/31) of evaluable subjects, and resulted in stable disease as best response in 18% (6/33) of patients with advanced pancreatic or colorectal cancer harboring KRAS mutations, including KRAS G12C (n=3), KRAS G12D (n=6), KRAS G12V (n=8), KRAS Q61L (n=1), and NRAS G12D (n=1) in patients with colorectal cancer (PMID: 29528991). | 29528991 |
| NRAS G12D | acute myeloid leukemia | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring NRAS G12D were sensitive to treatment with ASTX029 in culture (PMID: 34330842). | 34330842 | |
| NRAS G12D | melanoma | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of a melanoma cell line harboring NRAS G12D in culture (PMID: 34330842). | 34330842 | |
| NRAS G12D | acute myeloid leukemia | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PIK3CA inhibitor | Alpelisib + Binimetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Alpelisib (BYL719) inhibited proliferation in a human acute myeloid leukemia (AML) cell line harboring NRAS G12D in culture, and decreased disease burden in xenograft models (PMID: 24569456). | 24569456 |
| NRAS G12D | B-lymphoblastic leukemia/lymphoma | predicted - sensitive | Anti-CD19 CAR T cells | Case Reports/Case Series | Actionable | In a clinical case study, an investigational CD19-directed CAR T cells therapy resulted in rapid elimination of leukemic cells, including a subclone harboring NRAS G12D, in a patient with relapsed Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia, the NRAS G12D subclone remained undetectable at disease progression 6 weeks after treatment (PMID: 31905241). | 31905241 | |
| NRAS G12D | Advanced Solid Tumor | no benefit | NS1 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing NRAS G12D did not respond to treatment with NS1 in culture, resulting in sustained downstream signaling and cell transformation (PMID: 27820802). | 27820802 | |
| NRAS G12D | acute myeloid leukemia | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical | Actionable | In a preclinical study, Binimetinib (MEK162) inhibited growth of acute myeloid leukemia cells that have been demonstrated to harbor NRAS G12D in culture and decreased disease burden in xenograft models with NRAS G12D (PMID: 24569456, PMID: 11238126). | 24569456 11238126 |
| NRAS G12D | Advanced Solid Tumor | sensitive | N-Arachidonoyl Dopamine | Preclinical - Cell culture | Actionable | In a preclinical study, N-Arachidonoyl Dopamine (NADA) disrupted NRAS protein membrane localization and decreased NRAS downstream signaling, and inhibited proliferation and induced cell death in transformed cells expressing NRAS G12D in culture (PMID: 27760835). | 27760835 | |
| NRAS G12D | ovarian cancer | predicted - resistant | BI-3406 | Preclinical - Cell culture | Actionable | In a preclinical study, BI-3406 treatment failed to inhibit growth of ovarian cancer cells harboring NRAS G12D in culture (PMID: 32816843). | 32816843 | |
| KMT2A - MLLT1 NRAS G12D | acute myeloid leukemia | sensitive | Dinaciclib | Preclinical | Actionable | In a preclinical study, acute myeloid leukemia cells co-harboring KMT2A-MLLT1 and NRAS G12D demonstrated a decrease in tumor burden, reduced colony formation, and an increase in cell death when treated with Dinaciclib in both culture and mouse models (PMID: 26627013). | 26627013 | |
| KMT2A - MLLT1 NRAS G12D | acute myeloid leukemia | predicted - sensitive | AZ20 | Preclinical | Actionable | In a preclinical study, AZ20 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). | 27625305 | |
| KMT2A - MLLT1 NRAS G12D | acute myeloid leukemia | predicted - sensitive | AZD0156 | Preclinical | Actionable | In a preclinical study, AZD0156 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). | 27625305 | |
| 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 | 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 | |
| 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 | 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 | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 |
| 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 | |
| DNMT3A R882H NRAS G12D | acute myeloid leukemia | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | |
| KMT2A - MLLT3 NRAS G12D | leukemia | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of NRAS G12D in murine leukemia cells harboring KMT2A-MLLT3 resulted in increased sensitivity to treatment with PD-0325901 in culture (PMID: 33563661). | 33563661 |
| KMT2A - MLLT3 NRAS G12D | leukemia | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of NRAS G12D in murine leukemia cells harboring KMT2A-MLLT3 resulted in increased sensitivity to treatment with Mekinist (trametinib) in culture (PMID: 33563661). | 33563661 |
| NRAS exon4 | colon cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org). | detail... | |
| NRAS exon4 | colon cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org). | detail... | |
| NRAS exon4 | rectum cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 4 mutations (NCCN.org). | detail... | |
| NRAS exon4 | rectum cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 4 mutations (NCCN.org). | detail... | |
| NRAS A146X | colorectal cancer | resistant | Cetuximab | FDA contraindicated | Actionable | Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 4, codon 146 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS A146X | colorectal cancer | resistant | Panitumumab | FDA contraindicated | Actionable | Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 4, codon 146 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS G13D | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring NRAS G13D in culture (PMID: 26343583). | 26343583 | |
| NRAS G13D | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) resulted in durable tumor regression compared to stabilized tumor growth when treated with either agent alone in patient-derived xenograft (PDX) models of melanoma harboring NRAS G13D (PMID: 33318037). | 33318037 |
| NRAS G13D | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cells harboring NRAS G13D were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 | |
| NRAS G13D | adult T-cell leukemia/lymphoma | sensitive | RAS Inhibitor (Pan) | 3144 | Preclinical - Cell culture | Actionable | In a preclinical study, 3144 inhibited growth of patient-derived T-cell acute lymphocytic leukemia cells harboring NRAS G13D in culture (PMID: 28235199). | 28235199 |
| NRAS G13D | mantle cell lymphoma | sensitive | ERAS-007 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a mantle cell lymphoma cell line harboring NRAS G13D in culture and inhibited tumor growth in xenograft models (PMID: 34337566). | 34337566 | |
| NRAS G13D | B-cell acute lymphoblastic leukemia | no benefit | Everolimus | Case Reports/Case Series | Actionable | In a clinical study, a pediatric patient with relapsed B-cell acute lymphoblastic leukemia harboring NRAS G13D, who also harbored SETD2 L1778fs* and an IKZF1 deletion, was treated with Afinitor (everolimus) in combination with chemotherapy and experienced persistent disease, and the patient died 6 months later (PMID: 33563661; NCT02670525). | 33563661 | |
| NRAS G13D | mantle cell lymphoma | sensitive | PIK3CA inhibitor | Copanlisib + ERAS-007 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of ERAS-007 (ASN007) and Aliqopa (copanlisib) inhibited tumor growth in a cell line xenograft model of mantle cell lymphoma harboring NRAS G13D, and demonstrated improved efficacy over either agent alone (PMID: 34337566). | 34337566 |
| NRAS G13D | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cells harboring NRAS G13D in culture (PMID: 26343583). | 26343583 |
| NRAS G13D | melanoma | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of a melanoma cell line harboring NRAS G13D in culture (PMID: 34330842). | 34330842 | |
| NRAS G13X | colorectal cancer | resistant | Panitumumab | FDA contraindicated | Actionable | Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 2, codon 13 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS G13X | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | NRAS G13X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... | |
| NRAS G13X | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial (MATCH), Mektovi (binimetinib) treatment resulted in an objective response rate of 2.1% (1/47) that was deemed nonpromising in patients with advanced solid tumors harboring NRAS mutations at codon 12 (n=17), 13 (n=8), or 61 (n=22), with a 6-month progression-free survival (PFS) of 29.2%, a median PFS of 3.5 months, and a median overall survival of 10.5 months (PMID: 33637626; NCT02465060). | 33637626 |
| NRAS G13X | colorectal cancer | resistant | Cetuximab | FDA contraindicated | Actionable | Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 2, codon 13 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS A59X | colorectal cancer | resistant | Panitumumab | FDA contraindicated | Actionable | Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 3, codon 59 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS A59X | colorectal cancer | resistant | Cetuximab | FDA contraindicated | Actionable | Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 3, codon 59 mutations is contraindicated (FDA.gov). | detail... | |
| NRAS G115Efs*46 | colorectal cancer | predicted - resistant | Panitumumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, NRAS G115Efs*46 was identified at a frequency of >1% in 3 of 23 patients with metastatic colorectal cancer who did not respond to anti-EGFR therapy (Erbitux (cetuximab), n=12 or Vectibix (panitumumab), n=11), and was associated with a lack of response (p=0.029) to EGFR-targeted therapy (PMID: 32796636). | 32796636 | |
| NRAS G115Efs*46 | colorectal cancer | predicted - resistant | Cetuximab | Clinical Study - Cohort | Actionable | In a retrospective analysis, NRAS G115Efs*46 was identified at a frequency of >1% in 3 of 23 patients with metastatic colorectal cancer who did not respond to anti-EGFR therapy (Erbitux (cetuximab), n=12 or Vectibix (panitumumab), n=11), and was associated with a lack of response (p=0.029) to EGFR-targeted therapy (PMID: 32796636). | 32796636 | |
| NRAS mutant | melanoma | sensitive | CCT241161 | Preclinical | Actionable | In a preclinical study, CCT241161 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). | 25500121 | |
| NRAS mutant | melanoma | sensitive | PI3K Inhibitor (Pan) | Buparlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring an NRAS mutation resulted in inhibition of brain tumor growth and an improved survival benefit (PMID: 27307593). | 27307593 |
| NRAS mutant | melanoma | predicted - sensitive | Belvarafenib | Phase I | Actionable | In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in 44% (4/9) of patients with NRAS-mutant melanoma in a dose escalation study, and partial response in 22% (2/9) of NRAS-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). | detail... | |
| NRAS mutant | melanoma | predicted - sensitive | Belvarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Belvarafenib (HM95573) treatment resulted in an unconfirmed partial response in a patient with NRAS mutant melanoma (Journal of Clinical Oncology 34, no. 15_suppl (May 20 2016) 2570-2570; NCT02405065). | detail... | |
| NRAS mutant | multiple myeloma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | transitional cell carcinoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human urinary tract transitional cell carcinoma cells harboring mutant NRAS were moderately sensitive to Mekinist (trametinib) growth inhibition in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase III | Actionable | In a Phase III trial, Binimetinib (MEK162) treatment resulted in improved progression free survival (2.8 months), objective response rate (15%, 40/269) and disease control rate (58%, 156/269) compared to Deticene (dacarbazine) (1.5 months, 7%, 25%, respectively) in NRAS-mutant cutaneous melanoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9500)). | detail... |
| NRAS mutant | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Guideline | Actionable | Mektovi (binimetinib) is included in guidelines as second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring an NRAS mutation (NCCN.org). | detail... |
| NRAS mutant | thyroid gland cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase I | Actionable | In a Phase I study, selumetinib demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine; including patients with BRAF and NRAS mutations disease (PMID: 23406027). | 23406027 |
| NRAS mutant | colorectal cancer | no benefit | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) alone or in combination with chemotherapy is not indicated for use in patients with metastatic colorectal cancer harboring RAS mutations (PMID: 25190710; ESMO.org). | 25190710 detail... | |
| NRAS mutant | thyroid gland medullary carcinoma | sensitive | Cabozantinib | Guideline | Actionable | Cometriq (cabozantinib) is included in guidelines for patients with advanced or metastatic medullary thyroid carcinoma harboring RAS mutations (PMID: 31549998, PMID: 35491008; ESMO.org). | 35491008 31549998 detail... | |
| NRAS mutant | thyroid gland medullary carcinoma | sensitive | Cabozantinib | Phase III | Actionable | In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression-free survival (47 vs 8 weeks, HR 0.15, p=0.0317) compared to placebo in thyroid medullary carcinoma patients harboring RAS mutations (PMID: 27525386). | 27525386 | |
| NRAS mutant | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring a mutation in NRAS were resistant to Zelboraf (vemurafenib) mediated growth inhibition in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | colorectal cancer | no benefit | Cetuximab + Fluorouracil + Irinotecan + Leucovorin | Phase III | Actionable | In a retrospective analysis of a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI did not demonstrate an improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with RAS mutations (PMID: 25605843). | 25605843 | |
| NRAS mutant | melanoma | sensitive | Tubastatin A | Preclinical | Actionable | In a preclinical study, Tubastatin A inhibited proliferation of NRAS mutant melanoma cell lines in culture (PMID: 25957812). | 25957812 | |
| NRAS mutant | stomach carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | Erdheim-Chester disease | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). | detail... |
| NRAS mutant | Advanced Solid Tumor | no benefit | CC-90003 | Phase I | Actionable | In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (J Clin Oncol 35, 2017 (suppl; abstr 2577)). | detail... | |
| NRAS mutant | colorectal cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | colorectal cancer | no benefit | Regorafenib | Phase II | Actionable | In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). | 30120161 | |
| NRAS mutant | pancreatic cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | central nervous system cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human central nervous system cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | melanoma | predicted - sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring an NRAS mutation (PMID: 29247021). | 29247021 | |
| NRAS mutant | hepatocellular carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib + Sorafenib | Phase II | Actionable | In a Phase II trial, Refametinib (BAY86-9766) and Nexavar (sorafenib) combination treatment resulted in an objective response rate of 6.3% (1/16), a disease control rate of 43.8% (7/16), an overall survival of 12.7 months, and a progression-free survival of 1.5 months in patients unresectable or metastatic hepatocellular carcinoma harboring RAS (NRAS and KRAS) mutations (PMID: 29950351; NCT01915602). | 29950351 |
| NRAS mutant | melanoma | conflicting | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Ibrance (palbociclib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 | |
| NRAS mutant | melanoma | conflicting | Palbociclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ibrance (palbociclib) treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrated a lack of benefit (PMID: 27488531). | 27488531 | |
| NRAS mutant | colorectal cancer | no benefit | Cetuximab | Guideline | Actionable | Erbitux (cetuximab) alone or in combination with chemotherapy is not indicated for use in patients with metastatic colorectal cancer harboring RAS mutations (PMID: 25190710; ESMO.org). | 25190710 detail... | |
| NRAS mutant | acute myeloid leukemia | predicted - resistant | Pazopanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NRAS mutations correlated with resistance to Votrient (pazopanib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 | |
| NRAS mutant | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Belvarafenib + Cobimetinib | Phase I | Actionable | In a Phase I trial, Belvarafenib (HM95573) and Cotellic (cobimetinib) combination therapy was tolerable, and resulted in a response rate of 38% (5/13, 5 partial response) in patients with melanoma harboring NRAS mutations, with a median progression-free survival of 7.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 3007-3007; NCT03284502). | detail... |
| NRAS mutant | melanoma | sensitive | SBI-0640726 | Preclinical | Actionable | In a preclinical study, SBI-0640726 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). | 26603897 | |
| NRAS mutant | Advanced Solid Tumor | sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, cancer cell lines harboring NRAS mutations demonstrated increased sensitivity to RAF709 compared to NRAS wild-type cells in culture (PMID: 29343524). | 29343524 | |
| NRAS mutant | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + UNC2025 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of UNC2025 and Cotellic (cobimetinib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring an NRAS mutation in culture when compared to either therapy alone (PMID: 30482852). | 30482852 |
| NRAS mutant | acute myeloid leukemia | predicted - resistant | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NRAS mutations correlated with resistance to Zelboraf (vemurafenib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 | |
| NRAS mutant | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cell lines harboring an NRAS mutation were sensitive to the combination therapy of Ibrance (palbociclib) and Mekinist (trametinib) in culture, demonstrating reduced cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 |
| NRAS mutant | myelofibrosis | not applicable | N/A | Guideline | Prognostic | NRAS mutations are associated with decreased overall survival in patients with primary myelofibrosis (NCCN.org). | detail... | |
| NRAS mutant | neuroblastoma | 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 neuroblastoma cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). | 29437705 |
| NRAS mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | S63845 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in NRAS-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). | 27760111 |
| NRAS mutant | acute myeloid leukemia | predicted - resistant | Tivozanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NRAS mutations correlated with resistance to Fotivda (tivozanib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 | |
| NRAS mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Phase I | Actionable | In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease in 29% (2/7) of patients with NRAS mutated melanoma (PMID: 22805292; NCT00687622). | 22805292 |
| NRAS mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 |
| NRAS mutant | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase III | Actionable | In a Phase III clinical trial, treatment with Binimetinib (MEK162) improved median progression-free survival compared to treatment with Deticene (dacarbazine) (2.8 mo. vs. 1.5 mo.), but did not improve overall survival in patients with NRAS-mutant melanoma (PMID: 28284557). | 28284557 |
| NRAS mutant | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). | 23414587 |
| NRAS mutant | liver cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of liver cancer cell lines harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a partial response in 43% (6/14) and stable disease in 43% (6/14) of NRAS mutant melanoma patients (J Clin Oncol 32:5s, 2014 (Suppl;abstr 9009)). | detail... |
| NRAS mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a median progression-free survival of 6.7 months, a partial response in 25% (4/16), and stable disease in 44% (7/16) of NRAS mutant melanoma patients (J Clin Oncol 35, 2017 (suppl; abstr 9519)). | detail... |
| NRAS mutant | differentiated thyroid gland carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pazopanib + Trametinib | Phase I | Actionable | In a Phase I trial, of 10 differentiated thyroid cancer patients, 3 of 3 responders (all partial responses) to treatment with the combination of Votrient (pazopanib) and Mekinist (trametinib) harbored NRAS mutations, while none of the seven patients with stable disease or progressive disease had NRAS mutations (PMID: 31186313; NCT01438554). | 31186313 |
| NRAS mutant | lung non-small cell carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant non-small cell lung cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | melanoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | acute myeloid leukemia | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited proliferation of human NRAS mutant acute myeloid leukemia cell lines in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring an NRAS mutation (PMID: 27307593). | 27307593 |
| NRAS mutant | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrates a lack of benefit (PMID: 27488531). | 27488531 |
| NRAS mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in tumor regression in 33% (2/6) of melanoma xenograft models harboring an NRAS mutation (PMID: 27488531). | 27488531 |
| NRAS mutant | Advanced Solid Tumor | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). | detail... | |
| NRAS mutant | leukemia | sensitive | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) inhibited growth of NRAS mutant leukemia cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). | detail... | |
| NRAS mutant | autonomic nervous system neoplasm | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human autonomic ganglia cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | leukemia | 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 leukemia cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). | 29437705 |
| NRAS mutant | colon cancer | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, colon cancer cells harboring NRAS mutations were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). | 19276360 | |
| NRAS mutant | melanoma | sensitive | CCT196969 | Preclinical | Actionable | In a preclinical study, CCT196969 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). | 25500121 | |
| NRAS mutant | hematologic cancer | predicted - resistant | SHP099 | Preclinical | Actionable | In a preclinical study, hematopoietic cancer cell lines harboring NRAS mutations demonstrated resistance to SHP099 in cell culture (PMID: 27362227). | 27362227 | |
| NRAS mutant | lung adenocarcinoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human lung adenocarcinoma cell lines harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | sarcoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human sarcoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | biliary tract cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase I | Actionable | In a Phase I trial, Binimetinib (MEK162) treatment resulted in partial response in a biliary tract cancer patient harboring NRAS mutation (PMID: 28152546) | 28152546 |
| NRAS mutant | cervix carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | colorectal cancer | predicted - resistant | SYM004 | Preclinical - Pdx | Actionable | In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). | 29423521 | |
| NRAS mutant | acute myeloid leukemia | predicted - sensitive | AZD5153 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD5153 inhibited proliferation of acute myeloid leukemia cells harboring NRAS mutation in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27573426). | 27573426 | |
| NRAS mutant | Erdheim-Chester disease | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Guideline | Actionable | Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). | detail... |
| NRAS mutant | melanoma | sensitive | SBI-0640756 | Preclinical | Actionable | In a preclinical study, SBI-0640756 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). | 26603897 | |
| NRAS mutant | Advanced Solid Tumor | no benefit | LY3009120 | Case Reports/Case Series | Actionable | In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 1 of 5 patients with advanced or metastatic cancer harboring NRAS mutations (PMID: 31645440; NCT02014116). | 31645440 | |
| NRAS mutant | melanoma | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, NRAS mutations were associated with higher 6-month objective response rate (53.3% vs. 19.6% without NRAS mutations; p=0.019) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma, however, progression-free survival and overall survival were similar between patients with and without NRAS mutations (PMID: 29973670). | 29973670 | |
| NRAS mutant | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of ovarian cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | non-Hodgkin lymphoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human non-Hodgkin lymphoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Chloroquine + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Mekinist (trametinib) and Chloroquine resulted in tumor regression in a melanoma patient-derived xenograft (PDX) model harboring an NRAS mutation (PMID: 30833748). | 30833748 |
| NRAS mutant | melanoma | sensitive | BI-69A11 | Preclinical | Actionable | In a preclinical study, BI-69A11 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). | 26603897 | |
| NRAS mutant | melanoma | sensitive | Adavosertib | Preclinical | Actionable | In a preclinical study, Adavosertib (MK-1775) showed efficacy in NRAS mutant melanoma and in mutant KRAS colorectal, pancreatic, and lung cancers (PMID: 24791855). | 24791855 | |
| NRAS mutant | acute myeloid leukemia | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human acute myeloid leukemia cell lines harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | Advanced Solid Tumor | sensitive | Obatoclax | Preclinical | Actionable | In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with NRAS mutation in culture (PMID: 22460902). | 22460902 | |
| NRAS mutant | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited growth of NRAS mutant human melanoma cell lines in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | lymphoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human lymphoma cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | melanoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, NRAS mutations were associated with higher 6-month objective response rate (53.3% vs. 19.6% without NRAS mutations; p=0.019) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma, however, progression-free survival and overall survival were similar between patients with and without NRAS mutations (PMID: 29973670). | 29973670 | |
| NRAS mutant | leukemia | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Phase Ib/II | Actionable | In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). | detail... |
| BRAF wild-type NRAS mut | melanoma | sensitive | Lenvatinib | Phase I | Actionable | In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 83% (5/6) of melanoma patients harboring NRAS mutations and wild-type BRAF (PMID: 26169970). | 26169970 | |
| CDKN2A loss NRAS mut | melanoma | sensitive | Abemaciclib | Phase I | Actionable | In a Phase I trial, Abemaciclib (LY2835219) resulted in a partial response in a melanoma patient with CDKN2A loss and NRAS mutation (PMID: 27217383). | detail... 27217383 | |
| BRAF mut NRAS mut | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with BI-847325 inhibited growth of a BRAF-mutant melanoma cell line with BRAF-inhibitor resistance due to an NRAS mutation in culture (PMID: 25873592). | 25873592 |
| BRAF mut NRAS mut | melanoma | sensitive | Lenvatinib | Phase I | Actionable | In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 50% (1/2) of melanoma patients harboring both BRAF and NRAS mutations (PMID: 26169970). | 26169970 | |
| CTNNB1 mut NRAS mut | liver cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human liver cancer cells harboring mutant NRAS and mutant CTNNB1 were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| NRAS mut PIK3CA wild-type | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | TAK-733 | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cell lines harboring mutations in KRAS or NRAS and with wild-type PIK3CA demonstrated a trend toward increased sensitivity to TAK-733 in culture (PMID: 26439693). | 26439693 |
| NRAS mut PIK3CA H1047R | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing PIK3CA H1047R demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| NRAS mut PIK3CA E545K | melanoma | predicted - resistant | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, two of two NRAS-mutant melanoma cell lines expressing PIK3CA E545K demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 30819666). | 30819666 | |
| NRAS mut PIK3CA E545K | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, four of four NRAS-mutant melanoma cell lines expressing PIK3CA E545K were resistant to the combination treatment of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| NRAS mut PIK3CA E545K | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines expressing PIK3CA E545K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| NRAS mut TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + SAR405838 | Phase I | Actionable | In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). | 30585255 |
| NRAS mut TP53 mut | colorectal cancer | no benefit | Adavosertib | Phase II | Actionable | In a Phase II trial (FOCUS4-C), Adavosertib (AZD1775) treatment was well-tolerated and resulted in an advantage in progression-free survival (PFS, HR 0.40, p=0.0051) but not overall survival (0.92, p=0.93) compared to active monitoring in patients with metastatic colorectal cancer harboring both RAS and TP53 mutations, however, patients with NRAS mutations or KRAS non-G12/G13 mutations did not benefit from Adavosertib (AZD1775) treatment in subgroup PFS analysis (PMID: 34538072). | 34538072 | |
| NRAS wild-type | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, an NRAS wild-type melanoma cell line demonstrated inhibition of cell growth when treated with Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
| NRAS wild-type | rectum cancer | predicted - sensitive | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... | |
| NRAS wild-type | colon cancer | predicted - sensitive | Panitumumab | Guideline | Actionable | Vectibix (panitumumab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... | |
| NRAS wild-type | colorectal cancer | predicted - sensitive | Cetuximab + Fluorouracil + Irinotecan + Leucovorin | Phase III | Actionable | In a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI demonstrated a significant clinical benefit in OS, PFS, and objective response compared to FOLFIRI alone in colorectal cancer patients with RAS wild-type status (PMID: 25605843). | 25605843 | |
| NRAS wild-type | melanoma | sensitive | MEK1 Inhibitor | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with wild-type NRAS (PMID: 23039341). | 23039341 |
| NRAS wild-type | colon cancer | predicted - sensitive | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... | |
| NRAS wild-type | colorectal cancer | predicted - sensitive | Panitumumab | Phase III | Actionable | In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with RAS wild-type colorectal cancer compared to FOLFIRI treatment alone (PMID: 26341920). | 26341920 | |
| NRAS wild-type | colorectal cancer | predicted - sensitive | Panitumumab | FDA approved - On Companion Diagnostic | Actionable | Vectibix (panitumumab) is FDA approved for metastatic colorectal patients that are NRAS wild-type, as detected by a companion diagnostic (FDA.gov). | detail... detail... | |
| NRAS wild-type | melanoma | sensitive | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS wild-type melanoma cells demonstrated decreased cell viability when treated with Ibrance (palbociclib) in culture (PMID: 27488531). | 27488531 | |
| NRAS wild-type | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, an NRAS wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
| NRAS wild-type | rectum cancer | predicted - sensitive | Panitumumab | Guideline | Actionable | Vecitbix (pantitumumab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... | |
| BRAF mut NRAS wild-type | melanoma | sensitive | Lenvatinib | Phase I | Actionable | In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 100% (5/5) of melanoma patients harboring BRAF mutations and wild-type NRAS (PMID: 26169970). | 26169970 | |
| BRAF wild-type NRAS wild-type | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF wild-type NRAS wild-type | melanoma | sensitive | Lenvatinib | Phase I | Actionable | In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 44% (4/9) and partial response in 22% (2/9) of melanoma patients carrying wild-type BRAF and NRAS (PMID: 26169970). | 26169970 | |
| BRAF wild-type NRAS wild-type | melanoma | resistant | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to PLX7904 in culture (PMID: 27523909). | 27523909 | |
| BRAF wild-type NRAS wild-type | melanoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). | 27523909 | |
| BRAF wild-type NRAS wild-type | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line with wild-type BRAF and wild-type NRAS in culture (PMID: 27307593). | 27307593 |
| BRAF wild-type NRAS wild-type | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). | 27523909 |
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