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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS over exp melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Mektovi (binimetinib) treatment in melanoma cell lines with NRAS overexpression, but without NRAS or BRAF mutations, resulted in reduced downstream signaling and proliferation in cultured cells (PMID: 29245078). 29245078
FGFR1 amp NRAS over exp lung non-small cell carcinoma decreased response Infigratinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of Nras in FGFR1-amplified non-small cell lung carcinoma cells resulted in decreased response to Infigratinib (BGJ398) in culture (PMID: 28630215). 28630215
FGFR1 amp NRAS over exp lung non-small cell carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Infigratinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Infigratinib (BGJ398) and Mekinist (trametinib) combination treatment inhibited Erk signaling, resulting in growth inhibition in FGFR1-amplified non-small cell lung carcinoma cells overexpressing Nras in culture (PMID: 28630215). 28630215
BRAF V600E NRAS over exp colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, overexpression of wild-type NRAS in colorectal cancer cell lines harboring BRAF V600E induced Ras activation and Braf/Craf dimerization, conferred resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture and in cell line xenograft models (PMID: 28951457). 28951457
BRAF V600E NRAS over exp colorectal cancer sensitive BGB659 + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, BGB659 and Erbitux (cetuximab) combination treatment demonstrated enhanced inhibition of Erk phosphorylation and growth in BRAF V600E colorectal cancer cell lines overexpressing Nras in culture (PMID: 28951457). 28951457
NRAS 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 Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum 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 wild-type melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, an NRAS wild-type melanoma cell line demonstrated inhibition of cell growth when treated with Mekinist (trametinib) in culture (PMID: 27488531). 27488531
NRAS wild-type colorectal cancer predicted - sensitive Cetuximab + Fluorouracil + Irinotecan + Leucovorin Phase III Actionable In a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI demonstrated a significant clinical benefit in OS, PFS, and objective response compared to FOLFIRI alone in colorectal cancer patients with RAS wild-type status (PMID: 25605843). 25605843
NRAS wild-type melanoma sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, NRAS wild-type melanoma cells demonstrated decreased cell viability when treated with Ibrance (palbociclib) in culture (PMID: 27488531). 27488531
NRAS wild-type colorectal cancer predicted - sensitive Panitumumab Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with RAS wild-type colorectal cancer compared to FOLFIRI treatment alone (PMID: 26341920). 26341920
NRAS wild-type colorectal cancer predicted - sensitive Panitumumab FDA approved - On Companion Diagnostic Actionable Vectibix (panitumumab) is FDA approved for metastatic colorectal patients that are NRAS wild-type, as detected by a companion diagnostic (FDA.gov). detail... detail...
NRAS wild-type melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, an NRAS wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
NRAS wild-type melanoma sensitive MEK1 Inhibitor E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with wild-type NRAS (PMID: 23039341). 23039341
BRAF mut NRAS wild-type melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 100% (5/5) of melanoma patients harboring BRAF mutations and wild-type NRAS (PMID: 26169970). 26169970
BRAF wild-type NRAS wild-type melanoma resistant PLX7904 Preclinical - Cell culture Actionable In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to PLX7904 in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) Binimetinib + Buparlisib Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line with wild-type BRAF and wild-type NRAS in culture (PMID: 27307593). 27307593
BRAF wild-type NRAS wild-type melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 44% (4/9) and partial response in 22% (2/9) of melanoma patients carrying wild-type BRAF and NRAS (PMID: 26169970). 26169970
BRAF wild-type NRAS wild-type melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). 27523909
BRAF wild-type ERBB2 amp NRAS wild-type rectum cancer sensitive Pertuzumab + Trastuzumab Guideline Actionable Herceptin (trastuzumab) in combination with Perjeta (pertuzumab) is included in guidelines as second-line therapy for advanced or metastatic rectum cancer patients with ERBB2 amplification and wild-type NRAS and BRAF (NCCN.org). detail...
BRAF wild-type ERBB2 amp NRAS wild-type rectum cancer sensitive Lapatinib + Trastuzumab Guideline Actionable Herceptin (trastuzumab) in combination with Tykerb (lapatinib) is included in guidelines as second-line therapy for advanced or metastatic rectum cancer patients with ERBB2 amplification and wild-type NRAS and BRAF (NCCN.org). detail...
BRAF wild-type ERBB2 amp NRAS wild-type colon cancer sensitive Lapatinib + Trastuzumab Guideline Actionable Herceptin (trastuzumab) in combination with Tykerb (lapatinib) is included in guidelines as second-line therapy for advanced or metastatic colon cancer patients with ERBB2 amplification and NRAS, BBRAF wild-type (NCCN.org). detail...
BRAF wild-type ERBB2 amp NRAS wild-type colon cancer sensitive Pertuzumab + Trastuzumab Guideline Actionable Herceptin (trastuzumab) in combination with Perjeta (pertuzumab) is included in guidelines as second-line therapy for advanced or metastatic colon cancer patients with ERBB2 amplification and NRAS, BRAF wild-type (NCCN.org). detail...
NRAS exon2 colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org). detail...
NRAS exon2 colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org). detail...
NRAS exon2 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 2 mutations (NCCN.org). detail...
NRAS exon2 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 2 mutations (NCCN.org). detail...
NRAS Q61H rhabdomyosarcoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PIK3CA inhibitor Alpelisib + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in rhabdomyosarcoma cells harboring NRAS Q61H, demonstrating cell death in culture (PMID: 29437705). 29437705
NRAS 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 thyroid gland cancer sensitive MK2206 Preclinical - Cell culture Actionable In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an anaplastic thyroid cancer cell line harboring NRAS Q61R (PMID: 21289267). 21289267
AKT1 E17K NRAS Q61R bladder carcinoma sensitive BAY1125976 Preclinical - Cell culture Actionable In a preclinical study, BAY1125976 inhibited Akt activation and downstream signaling in bladder cancer cell lines carrying both Akt1 E17K and Nras Q61R mutations (AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3685). detail...
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R melanoma predicted - resistant Vemurafenib Clinical Study - Cohort Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistance-associated mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). 24265153
KIT D816V NRAS Q61R melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Pembrolizumab + Trametinib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring KIT D816V and NRAS Q61R demonstrated progressive disease when treated with a combination of Mekinist (trametinib) and Keytruda (pembrolizumab) (PMID: 28514312). 28514312
ATM mut NRAS Q61R melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring an ATM mutation and NRAS Q61R demonstrated a partial response and 16 month progression free survival when treated with Binimetinib (MEK162) (PMID: 28514312). 28514312
NRAS act mut lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a retrospective analysis, activating NRAS mutations were identified in 1 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). 31839416
CDKN2A mut NRAS act mut acute lymphoblastic leukemia resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human acute lymphoblastic leukemia cells harboring NRAS and CDKN2A mutations were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS G12V colorectal cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring NRAS G12V demonstrated resistance to Erbitux (cetuximab) in culture (PMID: 28179366). 28179366
NRAS G12V colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring NRAS G12V in culture (PMID: 28179366). 28179366
BRAF V600E NRAS G12V melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and over expressing NRAS G12V in culture (PMID: 26267534). 26267534
BRAF V600E NRAS G12V melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). 26267534
NRAS A146X colorectal cancer resistant Panitumumab FDA contraindicated Actionable Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 4, codon 146 mutations is contraindicated (FDA.gov). detail...
NRAS A146X colorectal cancer resistant Cetuximab FDA contraindicated Actionable Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 4, codon 146 mutations is contraindicated (FDA.gov). detail...
NRAS G12X colorectal cancer resistant Panitumumab FDA contraindicated Actionable Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 2, codon 12 mutations is contraindicated (FDA.gov). detail...
NRAS G12X myelodysplastic syndrome not applicable N/A Guideline Prognostic NRAS G12X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
NRAS G12X colorectal cancer resistant Cetuximab FDA contraindicated Actionable Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 2, codon 12 mutations is contraindicated (FDA.gov). detail...
NRAS amp melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Pdx Actionable In a preclinical study, Mektovi (binimetinib) treatment resulted in reduced tumor growth and proliferation in two patient-derived xenograft (PDX) melanoma models with NRAS copy number gain and without BRAF or NRAS mutations (PMID: 29245078). 29245078
FGFR1 amp NRAS amp lung non-small cell carcinoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring both FGFR1 and NRAS amplification were resistant to Mekinist (trametinib) in culture (PMID: 28630215). 28630215
FGFR1 amp NRAS amp lung non-small cell carcinoma resistant Infigratinib Preclinical - Cell culture Actionable In a preclinical study, amplification of NRAS was identified in a non-small cell lung cancer cell line harboring FGFR1 amplification that acquired resistance to Infigratinib (BGJ398) in culture (PMID: 28630215). 28630215
FGFR1 amp NRAS amp lung non-small cell carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Infigratinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Infigratinib (BGJ398) and Mekinist (trametinib) combination treatment inhibited Erk signaling, resulting in growth inhibition in non-small cell lung carcinoma cells harboring both FGFR1 and NRAS amplification in culture (PMID: 28630215). 28630215
BRAF V600E NRAS amp colorectal cancer predicted - resistant Panitumumab + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after achieving stable disease for 16 weeks with Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, NRAS amplification was identified as an acquired alteration at the time of progression (PMID: 28951457). 28951457
NRAS G13V adult T-cell leukemia sensitive RAS Inhibitor (Pan) 3144 Preclinical - Pdx & cell culture Actionable In a preclinical study, 3144 inhibited growth of patient-derived T-cell acute lymphocytic leukemia cells harboring NRAS G13V in culture, and reduced tumor burden in xenograft models (PMID: 28235199). 28235199
NRAS K117X colorectal cancer resistant Cetuximab FDA contraindicated Actionable Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 4, codon 117 mutations is contraindicated (FDA.gov). detail...
NRAS K117X colorectal cancer resistant Panitumumab FDA contraindicated Actionable Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 4, codon 117 mutations is contraindicated (FDA.gov). detail...
NRAS Q61X colorectal cancer resistant Panitumumab FDA contraindicated Actionable Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 3, codon 61 mutations is contraindicated (FDA.gov). detail...
NRAS Q61X 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 mutant skin melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase III Actionable In a Phase III trial, Binimetinib (MEK162) treatment resulted in improved progression free survival (2.8 months), objective response rate (15%, 40/269) and disease control rate (58%, 156/269) compared to Deticene (dacarbazine) (1.5 months, 7%, 25%, respectively) in NRAS-mutant cutaneous melanoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9500)). detail...
NRAS mutant skin melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Guideline Actionable Mektovi (binimetinib) is included in guidelines as second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring an NRAS mutation (NCCN.org). detail...
NRAS mutant ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of ovarian cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant 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 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 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 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 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 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 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 melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, PD-0325901 treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrates a lack of benefit (PMID: 27488531). 27488531
NRAS mutant hepatocellular carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Refametinib + Sorafenib Phase II Actionable In a Phase II trial, Refametinib (BAY86-9766) and Nexavar (sorafenib) combination treatment resulted in an objective response rate of 6.3% (1/16), a disease control rate of 43.8% (7/16), an overall survival of 12.7 months, and a progression-free survival of 1.5 months in patients unresectable or metastatic hepatocellular carcinoma harboring RAS (NRAS and KRAS) mutations (PMID: 29950351; NCT01915602). 29950351
NRAS mutant 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 sarcoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human sarcoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mutant acute myeloid leukemia predicted - resistant Tivozanib Preclinical - Patient cell culture Actionable In a preclinical study, NRAS mutations correlated with resistance to Tivozanib (AV-951) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
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 melanoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). 23414587
NRAS mutant melanoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase III Actionable In a Phase III clinical trial, treatment with Binimetinib (MEK162) improved median progression-free survival compared to treatment with Deticene (dacarbazine) (2.8 mo. vs. 1.5 mo.), but did not improve overall survival in patients with NRAS-mutant melanoma (PMID: 28284557). 28284557
NRAS mutant melanoma 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 Advanced Solid Tumor no benefit NS1 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing an NRAS mutation did not respond to treatment with NS1 in culture, resulting in sustained downstream signaling and cell transformation (PMID: 27820802). 27820802
NRAS mutant central nervous system cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human central nervous system cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant transitional cell carcinoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human urinary tract transitional cell carcinoma cells harboring mutant NRAS were moderately sensitive to Mekinist (trametinib) growth inhibition in culture (PMID: 26343583). 26343583
NRAS mutant 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 thyroid gland cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Phase I Actionable In a Phase I study, selumetinib demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine; including patients with BRAF and NRAS mutations disease (PMID: 23406027). 23406027
NRAS mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in tumor regression in 33% (2/6) of melanoma xenograft models harboring an NRAS mutation (PMID: 27488531). 27488531
NRAS mutant melanoma predicted - sensitive Belvarafenib Phase I Actionable In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in 44% (4/9) of patients with NRAS-mutant melanoma in a dose escalation study, and partial response in 22% (2/9) of NRAS-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). detail...
NRAS mutant melanoma predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a Phase I trial, Belvarafenib (HM95573) treatment resulted in an unconfirmed partial response in a patient with NRAS mutant melanoma (Journal of Clinical Oncology 34, no. 15_suppl (May 20 2016) 2570-2570; NCT02405065). detail...
NRAS mutant differentiated thyroid gland carcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Pazopanib + Trametinib Phase I Actionable In a Phase I trial, of 10 differentiated thyroid cancer patients, 3 of 3 responders (all partial responses) to treatment with the combination of Votrient (pazopanib) and Mekinist (trametinib) harbored NRAS mutations, while none of the seven patients with stable disease or progressive disease had NRAS mutations (PMID: 31186313; NCT01438554). 31186313
NRAS mutant acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human acute myeloid leukemia cell lines harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) Binimetinib + Buparlisib Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring an NRAS mutation (PMID: 27307593). 27307593
NRAS mutant melanoma sensitive PI3K Inhibitor (Pan) Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring an NRAS mutation resulted in inhibition of brain tumor growth and an improved survival benefit (PMID: 27307593). 27307593
NRAS mutant biliary tract cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase I Actionable In a Phase I trial, Binimetinib (MEK162) treatment resulted in partial response in a biliary tract cancer patient harboring NRAS mutation (PMID: 28152546) 28152546
NRAS mutant 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 acute myeloid leukemia predicted - resistant Vemurafenib Preclinical - Patient cell culture Actionable In a preclinical study, NRAS mutations correlated with resistance to Zelboraf (vemurafenib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
NRAS mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor S63845 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in NRAS-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). 27760111
NRAS mutant multiple myeloma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). 30819666
NRAS mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease in 29% (2/7) of patients with NRAS mutated melanoma (PMID: 22805292; NCT00687622). 22805292
NRAS mutant 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 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 leukemia predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Phase Ib/II Actionable In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). detail...
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 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 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 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 lymphoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human lymphoma cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant 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 lung adenocarcinoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human lung adenocarcinoma cell lines harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Ribociclib Phase Ib/II Actionable In a Phase Ib/II trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a partial response in 43% (6/14) and stable disease in 43% (6/14) of NRAS mutant melanoma patients (J Clin Oncol 32:5s, 2014 (Suppl;abstr 9009)). detail...
NRAS mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Ribociclib Phase Ib/II Actionable In a Phase Ib trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a median progression-free survival of 6.7 months, a partial response in 25% (4/16), and stable disease in 44% (7/16) of NRAS mutant melanoma patients (J Clin Oncol 35, 2017 (suppl; abstr 9519)). detail...
NRAS mutant autonomic nervous system neoplasm sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human autonomic ganglia cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant non-Hodgkin lymphoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human non-Hodgkin lymphoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mutant leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PIK3CA inhibitor Alpelisib + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in leukemia cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). 29437705
NRAS mutant 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 melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib + UNC2025 Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of UNC2025 and Cotellic (cobimetinib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring an NRAS mutation in culture when compared to either therapy alone (PMID: 30482852). 30482852
NRAS mutant 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 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 sensitive CCT241161 Preclinical Actionable In a preclinical study, CCT241161 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). 25500121
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 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 predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cell lines harboring an NRAS mutation were sensitive to the combination therapy of Ibrance (palbociclib) and Mekinist (trametinib) in culture, demonstrating reduced cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). 30819666
NRAS mutant 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 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 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 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 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 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 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 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 liver cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of liver cancer cell lines harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant neuroblastoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PIK3CA inhibitor Alpelisib + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in neuroblastoma cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). 29437705
NRAS mutant melanoma sensitive 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
BRAF wild-type NRAS mut melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 83% (5/6) of melanoma patients harboring NRAS mutations and wild-type BRAF (PMID: 26169970). 26169970
CDKN2A loss NRAS mut melanoma sensitive Abemaciclib Phase I Actionable In a Phase I trial, Abemaciclib (LY2835219) resulted in a partial response in a melanoma patient with CDKN2A loss and NRAS mutation (PMID: 27217383). detail... 27217383
BRAF mut NRAS mut melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 50% (1/2) of melanoma patients harboring both BRAF and NRAS mutations (PMID: 26169970). 26169970
BRAF mut NRAS mut melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI-847325 Preclinical - Cell culture Actionable In a preclinical study, treatment with BI-847325 inhibited growth of a BRAF-mutant melanoma cell line with BRAF-inhibitor resistance due to an NRAS mutation in culture (PMID: 25873592). 25873592
CTNNB1 mut NRAS mut liver cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human liver cancer cells harboring mutant NRAS and mutant CTNNB1 were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mut STAG2 dec exp melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in NRAS mutated melanoma cell lines resulted in decreased response to Mekinist (trametinib) in culture (PMID: 27500726). 27500726
NRAS mut PIK3CA wild-type colorectal cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor TAK-733 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cell lines harboring mutations in KRAS or NRAS and with wild-type PIK3CA demonstrated a trend toward increased sensitivity to TAK-733 in culture (PMID: 26439693). 26439693
AKT1 pos NRAS mut melanoma predicted - resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, two of two NRAS-mutant melanoma cell lines with AKT1 expression demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
AKT1 pos NRAS mut melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, two of four NRAS-mutant melanoma cell lines expressing AKT1 were resistant to the combination treatment of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 30819666). 30819666
AKT1 pos NRAS mut melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing AKT1 demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS mut PIK3CA H1047R melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing PIK3CA H1047R demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS mut PIK3CA E545K melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, four of four NRAS-mutant melanoma cell lines expressing PIK3CA E545K were resistant to the combination treatment of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS mut PIK3CA E545K melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cell lines expressing PIK3CA E545K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS mut PIK3CA E545K melanoma predicted - resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, two of two NRAS-mutant melanoma cell lines expressing PIK3CA E545K demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
NRAS Q61L NRAS mut melanoma decreased response Palbociclib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated a decreased response to treatment with Ibrance (palbociclib) in culture when compared to control (PMID: 30819666). 30819666
NRAS Q61L NRAS mut melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated resistance to the combination treatment with Mekinist (trametinib) and Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
NRAS Q61L NRAS mut melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS Q61K NRAS mut melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
NRAS Q61K NRAS mut melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS Q61K NRAS mut melanoma decreased response Palbociclib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated a decreased response to treatment with Ibrance (palbociclib) in culture compared to control (PMID: 30819666). 30819666
BRAF V600E MAP2K1 P387S NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma no benefit PI3K Inhibitor (Pan) Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma decreased response PI3K Inhibitor (Pan) GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive PI3K Inhibitor (Pan) Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma decreased response PI3K Inhibitor (Pan) GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were >10-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E 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 sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma decreased response PI3K Inhibitor (Pan) GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). 22389471
NRAS G115Efs*46 colorectal cancer predicted - resistant Panitumumab Clinical Study - Cohort Actionable In a retrospective analysis, NRAS G115Efs*46 was identified at a frequency of >1% in 3 of 23 patients with metastatic colorectal cancer who did not respond to anti-EGFR therapy (Erbitux (cetuximab), n=12 or Vectibix (panitumumab), n=11), and was associated with a lack of response (p=0.029) to EGFR-targeted therapy (PMID: 32796636). 32796636
NRAS G115Efs*46 colorectal cancer predicted - resistant Cetuximab Clinical Study - Cohort Actionable In a retrospective analysis, NRAS G115Efs*46 was identified at a frequency of >1% in 3 of 23 patients with metastatic colorectal cancer who did not respond to anti-EGFR therapy (Erbitux (cetuximab), n=12 or Vectibix (panitumumab), n=11), and was associated with a lack of response (p=0.029) to EGFR-targeted therapy (PMID: 32796636). 32796636
BRAF V600D NRAS dec exp melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600D and knockdown of NRAS demonstrated a decreased response to Mektovi (binimetinib) relative to cells without NRAS knockdown in culture (PMID: 29245078). 29245078
NRAS A59X colorectal cancer resistant Panitumumab FDA contraindicated Actionable Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 3, codon 59 mutations is contraindicated (FDA.gov). detail...
NRAS A59X colorectal cancer resistant Cetuximab FDA contraindicated Actionable Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 3, codon 59 mutations is contraindicated (FDA.gov). detail...
BRAF G596V NRAS G13R colorectal cancer sensitive Cetuximab + LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in a patient-derived xenograft model of colorectal cancer harboring BRAF G596V and NRAS G13R (PMID: 28611205). 28611205
BRAF V600E NRAS G13R colorectal cancer predicted - resistant PIK3CA inhibitor Alpelisib + Cetuximab + Encorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 24 weeks to Alpelisib (BYL719), Erbitux (cetuximab), and Braftovi (encorafenib) combination treatment, NRAS G13R was identified as an acquired mutation in liver metastasis at the time of progression (PMID: 28951457). 28951457
BRAF V600E NRAS G13R colorectal cancer predicted - sensitive BGB659 + Cetuximab Preclinical - Pdx Actionable In a preclinical study, BGB659 and Erbitux (cetuximab) combination treatment resulted in sustained inhibition of Mek and Erk phosphorylation, lead to tumor regression in patient-derived xenograft models of colorectal cancer harboring BRAF V600E and NRAS G13R (PMID: 28951457). 28951457
NRAS 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 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 + 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 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 + 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 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 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 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 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 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 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 predicted - resistant SHP099 Preclinical - Cell line xenograft Actionable In a preclinical study, neuroblastoma cell lines either harboring or expressing NRAS Q61K demonstrated resistance to treatment with SHP099, with increased cell viability and proliferation compared to wild-type Nras in culture, and moderate growth inhibition in cell line xenograft models compared when compared to combination therapies (PMID: 32586982). 32586982
NRAS Q61K lung cancer sensitive RAF709 Preclinical - Cell line xenograft Actionable In a preclinical study, RAF709 inhibited Erk signaling and proliferation of lung cancer cells harboring NRAS Q61K in culture, and resulted in tumor regression in cell line xenograft models (PMID: 29343524). 29343524
NRAS Q61K 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 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 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
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 lung adenocarcinoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). 29631033
BRAF V600E NRAS Q61K melanoma sensitive XL888 Preclinical Actionable In a preclinical study, treatment with XL888 resulted in increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant melanoma cells harboring BRAF V600E along with NRAS Q61K in cell culture (PMID: 22351686). 22351686
BRAF V600E NRAS Q61K melanoma resistant 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 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 MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
CDKN2A loss NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). 22983396
CDKN2A loss NRAS Q61K melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640726 delayed tumor growth of melanomas in mice with a genetic background of NRAS Q61K and CDKN2A loss (PMID: 26603897). 26603897
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response PI3K Inhibitor (Pan) GSK2126458 Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma conflicting PI3K Inhibitor (Pan) Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma 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 melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF 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 decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive PI3K Inhibitor (Pan) Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive PI3K Inhibitor (Pan) GSK2126458 Preclinical Actionable In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF G469R NRAS Q61K melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF G469R NRAS Q61K melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF 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 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 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 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 MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). 28783719
BRAF G469V NRAS Q61K melanoma 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 predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
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
NRAS G12D B-lymphoblastic leukemia/lymphoma with BCR-ABL1 predicted - sensitive Anti-CD19 CAR T cells Case Reports/Case Series Actionable In a clinical case study, an investigational CD19-directed CAR T cells therapy resulted in rapid elimination of leukemic cells, including a subclone harboring NRAS G12D, in a patient with relapsed Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia, the NRAS G12D subclone remained undetectable at disease progression 6 weeks after treatment (PMID: 31905241). 31905241
NRAS G12D Advanced Solid Tumor sensitive N-Arachidonoyl Dopamine Preclinical - Cell culture Actionable In a preclinical study, N-Arachidonoyl Dopamine (NADA) disrupted NRAS protein membrane localization and decreased NRAS downstream signaling, and inhibited proliferation and induced cell death in transformed cells expressing NRAS G12D in culture (PMID: 27760835). 27760835
NRAS G12D acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PIK3CA inhibitor Alpelisib + Binimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Alpelisib (BYL719) inhibited proliferation in a human acute myeloid leukemia (AML) cell line harboring NRAS G12D in culture, and decreased disease burden in xenograft models (PMID: 24569456). 24569456
NRAS G12D acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical Actionable In a preclinical study, Binimetinib (MEK162) inhibited growth of acute myeloid leukemia cells that have been demonstrated to harbor NRAS G12D in culture and decreased disease burden in xenograft models with NRAS G12D (PMID: 24569456, PMID: 11238126). 24569456 11238126
KMT2A - MLLT1 NRAS G12D acute myeloid leukemia predicted - sensitive AZ20 Preclinical Actionable In a preclinical study, AZ20 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). 27625305
KMT2A - MLLT1 NRAS G12D acute myeloid leukemia predicted - sensitive AZD0156 Preclinical Actionable In a preclinical study, AZD0156 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). 27625305
KMT2A - MLLT1 NRAS G12D acute myeloid leukemia sensitive Dinaciclib Preclinical Actionable In a preclinical study, acute myeloid leukemia cells co-harboring KMT2A-MLLT1 and NRAS G12D demonstrated a decrease in tumor burden, reduced colony formation, and an increase in cell death when treated with Dinaciclib in both culture and mouse models (PMID: 26627013). 26627013
BRAF D594G NRAS G12D melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
AKT1 E17K NRAS G12D prostate cancer sensitive BAY1125976 Preclinical - Cell line xenograft Actionable In a preclinical study, BAY1125976 inhibited proliferation of a prostate cancer cell line harboring AKT E17K and NRAS G12D in culture, and demonstrated antitumor activity in xenograft models (PMID: 27699769). 27699769
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive I-BET151 Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line harboring DNMT3A R882H and NRAS G12D mutations demonstrated reduced proliferation and downregulation of a DNMT3A R882H associated gene expression profile upon I-BET151 treatment in culture, and I-BET151 treatment delayed the onset of leukemia symptoms and improved survival in xenograft mouse models derived from these cells (PMID: 31164355). 31164355
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor I-BET151 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D treated with combined I-BET151 and Mekinist (trametinib) demonstrated impaired disease progression and improved survival superior to either therapy alone (PMID: 31164355). 31164355
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D was sensitive to Mekinist (trametinib), demonstrating impaired disease progression and improved survival (PMID: 31164355). 31164355
NRAS G13D melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring NRAS G13D in culture (PMID: 26343583). 26343583
NRAS G13D adult T-cell leukemia sensitive RAS Inhibitor (Pan) 3144 Preclinical - Cell culture Actionable In a preclinical study, 3144 inhibited growth of patient-derived T-cell acute lymphocytic leukemia cells harboring NRAS G13D in culture (PMID: 28235199). 28235199
NRAS G13D melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cells harboring NRAS G13D in culture (PMID: 26343583). 26343583
NRAS G13D melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cells harboring NRAS G13D were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
NRAS exon4 colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org). detail...
NRAS exon4 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 4 mutations (NCCN.org). detail...
NRAS exon4 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 4 mutations (NCCN.org). detail...
NRAS exon4 colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org). detail...
NRAS G13X myelodysplastic syndrome not applicable N/A Guideline Prognostic NRAS G13X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
NRAS G13X colorectal cancer resistant Panitumumab FDA contraindicated Actionable Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 2, codon 13 mutations is contraindicated (FDA.gov). detail...
NRAS G13X colorectal cancer resistant Cetuximab FDA contraindicated Actionable Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 2, codon 13 mutations is contraindicated (FDA.gov). detail...
NRAS 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 resistant PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 did not inhibit growth of melanoma cells harboring NRAS Q61L in culture or in cell line xenograft models (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma sensitive 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 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 decreased response LY3009120 Preclinical Actionable In a preclinical study, LY3009120 modestly inhibited soft agar growth of human melanoma cancer cells harboring NRAS Q61L in culture (PMID: 26343583). 26343583
NRAS Q61L melanoma sensitive 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 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 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
Clinical Trial Phase Therapies Title Recruitment Status