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Profile Name NRAS Q61K
Gene Variant Detail

NRAS Q61K (loss of function - predicted)

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

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 melanoma decreased response Lifirafenib + 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 melanoma decreased response Lifirafenib + 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 no benefit Lifirafenib + 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 melanoma no benefit Lifirafenib + 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 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 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
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 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 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 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 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 MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Lifirafenib + 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 lung non-small cell carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Lifirafenib + 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 thyroid cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 colorectal cancer 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 greater inhibition of tumor growth than either agent alone in a patient-derived xenograft (PDX) model of colorectal cancer harboring NRAS Q61K (PMID: 35913398). 35913398
NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Ribociclib Preclinical - Cell culture Actionable In a preclinical study, combination treatment with Mektovi (binimetinib) and Kisqali (ribociclib) resulted in greater inhibition cell growth compared to either agent alone in a melanoma cell line harboring NRAS Q61K in culture (PMID: 29496665). 29496665
NRAS Q61K colon cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, a colon cancer cell line expressing NRAS Q61K was resistant to Erbitux (cetuximab) in culture (PMID: 27636997). 27636997
NRAS Q61K colon cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) synergistically induced apoptosis and inhibited viability of a colon cancer cell line expressing NRAS Q61K in culture (PMID: 27636997). 27636997
NRAS Q61K colon cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Erbitux (cetuximab) and Koselugo (selumetinib) synergistically induced apoptosis and inhibited viability of a colon cancer cell line expressing NRAS Q61K in culture (PMID: 27636997). 27636997
NRAS Q61K colon cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Erbitux (cetuximab) and Pimasertib (MSC19363669B) synergistically induced apoptosis and inhibited proliferation and viability of a colon cancer cell line expressing NRAS Q61K in culture (PMID: 27636997). 27636997
NRAS Q61K neuroblastoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI-1347 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of BI-1347 to Mekinist (trametinib) resulted in enhanced growth inhibition of a neuroblastoma cell line harboring NRAS Q61K compared to Mekinist (trametinib) alone in culture (PMID: 36398965). 36398965
NRAS Q61K neuroblastoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI-1347 + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of BI-1347 and Koselugo (selumetinib) resulted in reduced tumor growth and improved survival compared to Koselugo (selumetinib) alone in a neuroblastoma cell line xenograft model harboring NRAS Q61K (PMID: 36398965). 36398965
NRAS Q61K melanoma predicted - sensitive BGB3245 Case Reports/Case Series Actionable In a Phase I trial, BGB3245 treatment demonstrated manageable safety and resulted in a disease control rate of 48% (16/33,1 complete response, 5 confirmed partial responses (PR), 2 unconfirmed PR, and 8 stable disease > 24 weeks) in patients with advanced solid tumors harboring MAPK pathway alterations, including a partial response in a patient with melanoma harboring NRAS Q61K (Cancer Res (2023) 83 (8_Supplement): CT031). detail...
NRAS Q61K lung non-small cell carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Lifirafenib + PD-0325901 Phase I Actionable In a Phase Ib trial, Lifirafenib (BGB-283) and PD-0325901 combination treatment demonstrated safety and activity in patients with advanced solid tumors harboring MAPK pathway alterations, resulting in an objective response rate of 27.8% (15/54, 1 complete and 14 partial responses), including an objective response in a patient with non-small cell lung cancer harboring NRAS Q61K (Cancer Res (2023) 83 (8_Supplement): CT033). detail...
NRAS Q61K neuroblastoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 4SC-205 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of 4SC-205 and Koselugo (selumetinib) inhibited viability to a greater degree than either therapy alone in a neuroblastoma cell line harboring NRAS Q61K (PMID: 34709738). 34709738
NRAS Q61K melanoma predicted - sensitive MEK inhibitor (Pan) Tunlametinib Case Reports/Case Series Actionable In a Phase II trial, Tunlametinib (HL-085) treatment resulted in a confirmed objective response rate of 35.8% (34/95, all partial responses), a median progression-free survival of 4.2 months, disease control rate of 72.6% (69/95), median duration of response of 6.1 months, and median overall survival of 13.7 months in Chinese patients with advanced melanoma harboring NRAS mutations including NRAS Q61R (40%), Q61K (29.5%), and G12D (9.5%) (PMID: 38479118; NCT05217303). 38479118
NRAS Q61K thyroid cancer sensitive IHMT-RAF-128 Preclinical - Cell culture Actionable In a preclinical study, IHMT-RAF-128 inhibited proliferation in a thyroid cancer cell line harboring NRAS Q61K in culture (PMID: 37164118). 37164118
NRAS Q61K ameloblastoma sensitive MEK inhibitor (Pan) GDC-0623 Preclinical - Cell culture Actionable In a preclinical study, GDC-0623 inhibited Erk phosphorylation and viability of an ameloblastoma cell line harboring NRAS Q61K in culture (PMID: 35689405). 35689405
NRAS Q61K anaplastic thyroid carcinoma sensitive Ravoxertinib Preclinical - Cell culture Actionable In a preclinical study, Ravoxertinib (GDC-0994) inhibited viability of an anaplastic thyroid carcinoma cell line harboring NRAS Q61K in culture (PMID: 38728872). 38728872
NRAS Q61K neuroblastoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Ganitumab + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of Ganitumab (AMG-479) and Mekinist (trametinib) synergistically inhibited viability of two neuroblastoma cell lines harboring NRAS Q61K culture, and delayed tumor growth and enhanced survival in a cell line xenograft model (PMID: 39001383). 39001383
NRAS Q61K ovary adenocarcinoma predicted - sensitive ASTX029 Case Reports/Case Series Actionable In a Phase II trial, ASTX029 treatment was well tolerated in patients with relapsed/refractory gynecological tumors harboring MAPK pathway alterations, and resulted in an objective response rate of 12.5% (4/32, all partial responses), a median duration of response of 8.5 months, and a median overall survival of 11.2 months, with a partial response in a patient with ovarian adenocarcinoma harboring NRAS Q61K who progressed on prior MEKi therapy (Ann Oncol (2024) 35 (Suppl_2): S591; NCT03520075). detail...