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Profile Name NRAS Q61L
Gene Variant Detail

NRAS Q61L (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 Q61L melanoma sensitive CCT241161 Preclinical - Cell line xenograft Actionable In a preclinical study, CCT241161 inhibited MEK and ERK activation and growth of a melanoma cell line harboring NRAS Q61L in culture, and inhibited tumor growth in a NRAS Q61L-mutant melanoma cell line xenograft model (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma sensitive CCT196969 Preclinical - Cell line xenograft Actionable In a preclinical study, CCT196969 inhibited MEK and ERK activation and growth of a melanoma cell line harboring NRAS Q61L in culture, and inhibited tumor growth in a NRAS Q61L-mutant melanoma cell line xenograft model (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma resistant PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 did not inhibit growth of melanoma cells harboring NRAS Q61L in culture or in cell line xenograft models (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma decreased response LY3009120 Preclinical Actionable In a preclinical study, LY3009120 modestly inhibited soft agar growth of human melanoma cancer cells harboring NRAS Q61L in culture (PMID: 26343583). 26343583
NRAS Q61L melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring NRAS Q61L in culture (PMID: 26343583). 26343583
NRAS Q61L melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cells harboring NRAS Q61L were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
NRAS Q61L melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). 23414587
NRAS Q61L melanoma sensitive RAF709 Preclinical - Cell culture Actionable In a preclinical study, RAF709 inhibited Erk signaling and proliferation of melanoma cells harboring NRAS Q61L in culture (PMID: 29343524). 29343524
NRAS Q61L acute myeloid leukemia predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, PD-0325901 treatment induced apoptosis and inhibited proliferation of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 28923853). 28923853
NRAS Q61L acute myeloid leukemia no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, addition of Nexavar (sorafenib) to PD-0325901 treatment did not demonstrate increased sensitivity compared to PD-0325901 alone in an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 28923853). 28923853
NRAS Q61L melanoma sensitive Chelidonine Preclinical - Cell line xenograft Actionable In a preclinical study, Chelidonine treatment inhibited activation of Nras and downstream signaling pathways, reduced proliferation and colony formation, and induced apoptosis in melanoma cells harboring NRAS Q61L in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 32156748). 32156748
NRAS Q61L 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 Q61L in culture resulted in a decreased response compared to the combination treatment with Lifirafenib (BGB-283) and Mekinist (trametinib), demonstrating reduced inhibition of cell growth (PMID: 33318037). 33318037
NRAS Q61L melanoma 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 Q61L in culture resulted in a decreased response compared to the combination treatment with Lifirafenib (BGB-283) and Mekinist (trametinib), demonstrating reduced inhibition of cell growth (PMID: 33318037). 33318037
NRAS Q61L melanoma no benefit 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 Q61L in culture (PMID: 33318037). 33318037
NRAS Q61L 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 Q61L in culture (PMID: 33318037). 33318037
NRAS Q61L melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + RAF709 Preclinical - Cell culture Actionable In a preclinical study, the combination of Mektovi (binimetinib) and RAF709 resulted in inhibition of cell growth in a MEK inhibitor-resistant melanoma cell line harboring NRAS Q61L (PMID: 33318037). 33318037
NRAS Q61L melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Belvarafenib + Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of Cotellic (cobimetinib) to treatment with Belvarafenib (HM95573) in melanoma cell lines harboring NRAS Q61L resulted in greater inhibition of cell proliferation in culture compared to single agent alone, and led to decreased tumor volume, with increased efficacy and response durability in a cell line xenograft model (PMID: 33953400). 33953400
NRAS Q61L melanoma predicted - sensitive LY3214996 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring NRAS Q61L was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895). 31744895
NRAS Q61L liver cancer sensitive ERAS-007 Preclinical - Cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a liver cancer cell line harboring NRAS Q61L in culture (PMID: 34337566). 34337566
NRAS Q61L acute myeloid leukemia sensitive ASTX029 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring NRAS Q61L were sensitive to treatment with ASTX029 in culture (PMID: 34330842). 34330842
NRAS Q61L urinary bladder cancer sensitive RAF265 Preclinical - Cell culture Actionable In a preclinical study, RAF265 treatment decreased colony formation of a bladder cancer cell line harboring NRAS Q61L in culture (PMID: 34554931). 34554931
NRAS Q61L urinary bladder cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF265 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, RAF265 and Mekinist (trametinib) combination treatment inhibited colony formation compared to RAF265 alone in cultured cells harboring NRAS Q61L (PMID: 34554931). 34554931
NRAS Q61L rhabdomyosarcoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and LY3009120 combination treatment synergistically inhibited Erk phosphorylation, proliferation, and colony formation and induced cell cycle arrest and apoptosis in a rhabdomyosarcoma cell line harboring NRAS Q61L in culture (PMID: 34737198). 34737198
NRAS Q61L rhabdomyosarcoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3214996 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and LY3214996 combination treatment synergistically inhibited growth and induced apoptosis and cell cycle arrest in a rhabdomyosarcoma cell line harboring NRAS Q61L in culture (PMID: 34737198). 34737198
NRAS Q61L rhabdomyosarcoma sensitive LY3009120 + LY3214996 Preclinical - Cell culture Actionable In a preclinical study, LY3214996 and LY3009120 combination treatment synergistically induced cell cycle arrest and apoptosis in rhabdomyosarcoma cell lines harboring NRAS Q61L in culture (PMID: 34737198). 34737198
NRAS Q61L 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 Q61L in culture (PMID: 29496665). 29496665
NRAS Q61L acute myeloid leukemia resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cell lines harboring NRAS Q61L were resistant to RMC-4550 treatment in culture (PMID: 37992684). 37992684
NRAS Q61L mucosal melanoma predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a clinical case study, Belvarafenib (HM95573) treatment resulted in a partial response with a progression-free survival of 6.2 months in a mucosal melanoma patient harboring NRAS Q61L (PMID: 38470950). 38470950
NRAS Q61L melanoma sensitive MEK inhibitor (Pan) NST-628 Preclinical - Cell line xenograft Actionable In a preclinical study, NST-628 inhibited viability of a melanoma cancer cell line harboring NRAS Q61L in culture and inhibited tumor growth and induced tumor regression in a cell line xenograft model (PMID: 38588399). 38588399
NRAS Q61L acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AMG 176 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and Tapotoclax (AMG 176) synergistically inhibited viability of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 38456804). 38456804
NRAS Q61L acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD5991 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and AZD5991 synergistically inhibited viability of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 38456804). 38456804
NRAS Q61L acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AMG 176 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) and Tapotoclax (AMG 176) synergistically inhibited viability of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 38456804). 38456804
NRAS Q61L acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD5991 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) and AZD5991 synergistically inhibited viability of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 38456804). 38456804
NRAS Q61L acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BCL201 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) and BCL201 (S55746) synergistically inhibited viability of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 38456804). 38456804
NRAS Q61L acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and Venclexta (venetoclax) synergistically inhibited viability of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 38456804). 38456804
NRAS Q61L acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) and Venclexta (venetoclax) synergistically inhibited viability of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 38456804). 38456804