Gene Variant Detail

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Gene NRAS
Variant Q61K
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions NRAS Q61K is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61K results in activation of downstream pathway signaling, increased survival, and transformation of cultured cells (PMID: 22718121, PMID: 34117033), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS Q61K (PMID: 3510078).
Associated Drug Resistance

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Transcript NM_002524.4
gDNA chr1:g.114713909G>T
cDNA c.181C>A
Protein p.Q61K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524.4 chr1:g.114713909G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_002524 chr1:g.114713909G>T c.181C>A p.Q61K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 melanoma sensitive 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 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 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 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 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 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 sensitive 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 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 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 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 lung non-small cell carcinoma sensitive 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 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 colorectal cancer predicted - sensitive 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
NRAS Q61K lung non-small cell carcinoma sensitive 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 neuroblastoma sensitive 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 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 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 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 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 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 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 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 lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma decreased response 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 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 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 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 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 lung non-small cell carcinoma sensitive 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 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 predicted - sensitive 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 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 lung non-small cell carcinoma sensitive 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 thyroid gland cancer predicted - sensitive Everolimus + RO5126766 Case Reports/Case Series Actionable In a Phase I trial, the combination of Afinitor (everolimus) and RO5126766 (VS-6766) resulted in a partial response in a patient with thyroid cancer harboring NRAS Q61K (Journal of Clinical Oncology 2022 40:16_suppl, 9018-9018; NCT02407509). detail...
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 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 lung non-small cell carcinoma sensitive 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 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
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 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 sensitive 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 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 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
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
CDKN2A loss NRAS Q61K melanoma sensitive 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 decreased response 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 decreased response 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 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 conflicting 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 sensitive 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 sensitive 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 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 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 decreased response 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 V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant 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 V600K NRAS Q61K melanoma sensitive 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 sensitive 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 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 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 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 decreased response 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 V600E NRAS Q61K NRAS A146T melanoma sensitive 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 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 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 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 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 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 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 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 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 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 G466V NRAS Q61K lung non-small cell carcinoma sensitive 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 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 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 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
BRAF G469V NRAS Q61K melanoma predicted - resistant 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 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
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 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
NRAS Q61K NRAS mut melanoma predicted - resistant 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 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
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 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
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia predicted - sensitive FF-10101 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of FF-10101 and Mekinist (trametinib) resulted in decreased viability of acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K compared to treatment with FF-10101 alone in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia predicted - sensitive FF-10101 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of FF-10101 and Mekinist (trametinib) resulted in decreased viability of acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C compared to treatment with FF-10101 alone in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 35395091). 35395091
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS act mut melanoma predicted - sensitive 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 melanoma predicted - sensitive Binimetinib + KIN-2787 Preclinical - Cell line xenograft Actionable In a preclinical study, KIN-2787 and Mektovi (binimetinib) combination treatment inhibited growth of melanoma cell lines harboring NRAS mutations in culture, and resulted in improved tumor growth inhibition and Mapk pathway suppression in cell line xenograft models compared to either agent alone (J Clin Oncol 40, 2022 (suppl 16; abstr e15099)). 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
NRAS act mut Advanced Solid Tumor no benefit 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 mutant lung adenocarcinoma resistant 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 liver cancer sensitive 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 non-Hodgkin lymphoma resistant 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 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 lymphoma sensitive 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 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 leukemia sensitive 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 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 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 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 central nervous system cancer sensitive 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 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 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 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 hepatocellular carcinoma sensitive 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 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 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 autonomic nervous system neoplasm sensitive 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 ovarian cancer sensitive 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 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 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 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 multiple myeloma sensitive 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 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 transitional cell carcinoma decreased response 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 melanoma sensitive 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 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 sensitive 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 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 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 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 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 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 Erdheim-Chester disease sensitive 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, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). detail...
NRAS mutant biliary tract cancer predicted - sensitive 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 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 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 melanoma sensitive 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 leukemia predicted - sensitive 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...
NRAS mutant melanoma no benefit 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 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 melanoma conflicting 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 melanoma conflicting 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 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 melanoma predicted - sensitive 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 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 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 acute myeloid leukemia sensitive 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 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 thyroid gland cancer sensitive 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 neuroblastoma sensitive 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 sarcoma resistant 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 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 melanoma predicted - sensitive 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 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 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 melanoma sensitive 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 skin melanoma sensitive 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 skin melanoma sensitive 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 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 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 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 melanoma predicted - sensitive 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 melanoma sensitive 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 sensitive 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 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 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 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 LXH 254 + Trametinib Phase I Actionable In a Phase Ib trial, combination treatment with LXH 254 and Mekinist (trametinib) resulted in an overall response rate of 30% (9/30) and stable disease in 43.3% (13/30) of patients with melanoma harboring NRAS mutations (Cancer Res 2022;82(12_Suppl):Abstract nr CT197; NCT02974725). detail...
NRAS mutant Erdheim-Chester disease sensitive 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, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). detail...
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 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 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 differentiated thyroid gland carcinoma predicted - sensitive 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 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 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 Q61X melanoma sensitive 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 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 colorectal cancer unknown 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 Q61X Advanced Solid Tumor unknown 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 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 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 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 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...