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Profile Name NRAS Q61R
Gene Variant Detail

NRAS Q61R (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 Q61R thyroid 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 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 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 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 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 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 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 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 MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Lifirafenib + 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 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 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 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 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 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 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 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 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 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 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 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 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
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 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 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 melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor IMM-1-104 Preclinical - Cell line xenograft Actionable In a preclinical study, IMM-1-104 treatment led to tumor growth regression in a cell line xenograft model of melanoma harboring NRAS Q61R (Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P252). detail...
NRAS Q61R melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, PD-0325901 treatment induced cell cycle arrest and inhibited growth of melanoma cells harboring NRAS Q61R in culture (PMID: 25422890). 25422890
NRAS Q61R melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RO5126766 Preclinical - Cell line xenograft Actionable In a preclinical study, RO5126766 (VS-6766) treatment induced cell cycle arrest, decreased Mek and Erk phosphorylation, and inhibited growth of melanoma cells harboring NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 25422890). 25422890
NRAS Q61R melanoma predicted - sensitive MEK inhibitor (Pan) Tunlametinib Case Reports/Case Series Actionable In a Phase I trial, Tunlametinib (HL-085) treatment demonstrated safety and preliminary efficacy in patients with advanced melanoma harboring NRAS mutations, resulting in an objective response rate of 37.5% (3/8), a disease control rate of 75% (6/8), and a median progression-free survival of 114.0 days in patients harboring NRAS Q61R at the recommended Phase II dose (PMID: 36600247; NCT03973151). 36600247
NRAS Q61R melanoma predicted - sensitive PHI-501 Preclinical - Cell culture Actionable In a preclinical study, PHI-501 inhibited growth and migration and induced apoptosis in a melanoma cell line harboring NRAS Q61R in culture (Cancer Res (2023) 83 (7_Supplement): 1627). detail...
NRAS Q61R 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 34.7%, a median progression-free survival of 4.2 months, and 1-year survival rate of 57.2% in patients with advanced melanoma harboring NRAS mutations including NRAS Q61R (40%), Q61K (29.5%), and G12D (9.5%) (J Clin Oncol 41, 2023 (suppl 16; abstr 9510); NCT05217303). detail...