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| Gene | NRAS |
| Variant | mutant |
| Impact List | unknown |
| Protein Effect | unknown |
| Gene Variant Descriptions | NRAS mutant indicates an unspecified mutation in the NRAS gene. |
| Associated Drug Resistance |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 | lung adenocarcinoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human lung adenocarcinoma cell lines harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | ovarian cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of ovarian cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | 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 | 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 | non-Hodgkin lymphoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human non-Hodgkin lymphoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | 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 | 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 | melanoma | sensitive | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring an NRAS mutation (PMID: 27307593). | 27307593 |
| NRAS mutant | Advanced Solid Tumor | 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 | hepatocellular carcinoma | sensitive | Refametinib + Sorafenib | Phase II | Actionable | In a Phase II trial, Refametinib (BAY86-9766) and Nexavar (sorafenib) combination treatment resulted in an objective response rate of 6.3% (1/16), a disease control rate of 43.8% (7/16), an overall survival of 12.7 months, and a progression-free survival of 1.5 months in patients unresectable or metastatic hepatocellular carcinoma harboring RAS (NRAS and KRAS) mutations (PMID: 29950351; NCT01915602). | 29950351 |
| NRAS mutant | melanoma | sensitive | Buparlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring an NRAS mutation resulted in inhibition of brain tumor growth and an improved survival benefit (PMID: 27307593). | 27307593 |
| NRAS mutant | biliary tract cancer | predicted - sensitive | Binimetinib | Phase I | Actionable | In a Phase I trial, Binimetinib (MEK162) treatment resulted in partial response in a biliary tract cancer patient harboring NRAS mutation (PMID: 28152546) | 28152546 |
| NRAS mutant | 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 | colorectal cancer | no benefit | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) alone or in combination with chemotherapy is not indicated for use in patients with metastatic colorectal cancer harboring RAS mutations (PMID: 25190710; ESMO.org). | 25190710 detail... |
| NRAS mutant | multiple myeloma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | leukemia | sensitive | Alpelisib + Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in leukemia cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). | 29437705 |
| NRAS mutant | 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 | skin melanoma | sensitive | Binimetinib | Phase III | Actionable | In a Phase III trial, Binimetinib (MEK162) treatment resulted in improved progression free survival (2.8 months), objective response rate (15%, 40/269) and disease control rate (58%, 156/269) compared to Deticene (dacarbazine) (1.5 months, 7%, 25%, respectively) in NRAS-mutant cutaneous melanoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9500)). | detail... |
| NRAS mutant | skin melanoma | sensitive | Binimetinib | Guideline | Actionable | Mektovi (binimetinib) is included in guidelines as second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring an NRAS mutation (NCCN.org). | detail... |
| NRAS mutant | differentiated thyroid gland carcinoma | predicted - sensitive | Pazopanib + Trametinib | Phase I | Actionable | In a Phase I trial, of 10 differentiated thyroid cancer patients, 3 of 3 responders (all partial responses) to treatment with the combination of Votrient (pazopanib) and Mekinist (trametinib) harbored NRAS mutations, while none of the seven patients with stable disease or progressive disease had NRAS mutations (PMID: 31186313; NCT01438554). | 31186313 |
| NRAS mutant | neuroblastoma | sensitive | Alpelisib + Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in neuroblastoma cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). | 29437705 |
| NRAS mutant | melanoma | no benefit | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrates a lack of benefit (PMID: 27488531). | 27488531 |
| NRAS mutant | 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 | acute myeloid leukemia | predicted - resistant | Tivozanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NRAS mutations correlated with resistance to Fotivda (tivozanib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 |
| NRAS mutant | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring a mutation in NRAS were resistant to Zelboraf (vemurafenib) mediated growth inhibition in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | melanoma | sensitive | Adavosertib | Preclinical | Actionable | In a preclinical study, Adavosertib (MK-1775) showed efficacy in NRAS mutant melanoma and in mutant KRAS colorectal, pancreatic, and lung cancers (PMID: 24791855). | 24791855 |
| NRAS mutant | melanoma | sensitive | Palbociclib + PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in tumor regression in 33% (2/6) of melanoma xenograft models harboring an NRAS mutation (PMID: 27488531). | 27488531 |
| NRAS mutant | 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 | Erdheim-Chester disease | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). | detail... |
| NRAS mutant | Erdheim-Chester disease | sensitive | Cobimetinib | Guideline | Actionable | Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). | detail... |
| NRAS mutant | melanoma | conflicting | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Ibrance (palbociclib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 |
| NRAS mutant | melanoma | conflicting | Palbociclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ibrance (palbociclib) treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrated a lack of benefit (PMID: 27488531). | 27488531 |
| NRAS mutant | melanoma | sensitive | CCT196969 | Preclinical | Actionable | In a preclinical study, CCT196969 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). | 25500121 |
| NRAS mutant | acute myeloid leukemia | predicted - sensitive | AZD5153 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD5153 inhibited proliferation of acute myeloid leukemia cells harboring NRAS mutation in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27573426). | 27573426 |
| NRAS mutant | 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 | 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 | melanoma | sensitive | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a partial response in 43% (6/14) and stable disease in 43% (6/14) of NRAS mutant melanoma patients (J Clin Oncol 32:5s, 2014 (Suppl;abstr 9009)). | detail... |
| NRAS mutant | melanoma | sensitive | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a median progression-free survival of 6.7 months, a partial response in 25% (4/16), and stable disease in 44% (7/16) of NRAS mutant melanoma patients (J Clin Oncol 35, 2017 (suppl; abstr 9519)). | detail... |
| NRAS mutant | 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 | 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 | central nervous system cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human central nervous system cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | 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 | sensitive | S63845 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in NRAS-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). | 27760111 |
| NRAS mutant | melanoma | predicted - sensitive | Cobimetinib + UNC2025 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of UNC2025 and Cotellic (cobimetinib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring an NRAS mutation in culture when compared to either therapy alone (PMID: 30482852). | 30482852 |
| NRAS mutant | 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 | 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 | 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 | 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 | Belvarafenib + Cobimetinib | Phase I | Actionable | In a Phase I trial, Belvarafenib (HM95573) and Cotellic (cobimetinib) combination therapy was tolerable, and resulted in a response rate of 38% (5/13, 5 partial response) in patients with melanoma harboring NRAS mutations, with a median progression-free survival of 7.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 3007-3007; NCT03284502). | detail... |
| NRAS mutant | melanoma | sensitive | SBI-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 | colorectal cancer | no benefit | Cetuximab | Guideline | Actionable | Erbitux (cetuximab) alone or in combination with chemotherapy is not indicated for use in patients with metastatic colorectal cancer harboring RAS mutations (PMID: 25190710; ESMO.org). | 25190710 detail... |
| NRAS mutant | melanoma | predicted - sensitive | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cell lines harboring an NRAS mutation were sensitive to the combination therapy of Ibrance (palbociclib) and Mekinist (trametinib) in culture, demonstrating reduced cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 |
| NRAS mutant | melanoma | sensitive | CCT241161 | Preclinical | Actionable | In a preclinical study, CCT241161 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). | 25500121 |
| NRAS mutant | melanoma | conflicting | Binimetinib | Phase II | Actionable | In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). | 23414587 |
| NRAS mutant | melanoma | conflicting | Binimetinib | Phase III | Actionable | In a Phase III clinical trial, treatment with Binimetinib (MEK162) improved median progression-free survival compared to treatment with Deticene (dacarbazine) (2.8 mo. vs. 1.5 mo.), but did not improve overall survival in patients with NRAS-mutant melanoma (PMID: 28284557). | 28284557 |
| NRAS mutant | leukemia | predicted - sensitive | Trametinib | Phase Ib/II | Actionable | In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). | detail... |
| NRAS mutant | autonomic nervous system neoplasm | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human autonomic ganglia cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | 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 | 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 | 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 | 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 | 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 | melanoma | sensitive | Chloroquine + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Mekinist (trametinib) and Chloroquine resulted in tumor regression in a melanoma patient-derived xenograft (PDX) model harboring an NRAS mutation (PMID: 30833748). | 30833748 |
| NRAS mutant | myelofibrosis | not applicable | N/A | Guideline | Prognostic | NRAS mutations are associated with decreased overall survival in patients with primary myelofibrosis (NCCN.org). | detail... |
| NRAS mutant | transitional cell carcinoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, human urinary tract transitional cell carcinoma cells harboring mutant NRAS were moderately sensitive to Mekinist (trametinib) growth inhibition in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | colorectal cancer | no benefit | Cetuximab + Fluorouracil + Irinotecan + Leucovorin | Phase III | Actionable | In a retrospective analysis of a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI did not demonstrate an improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with RAS mutations (PMID: 25605843). | 25605843 |
| NRAS mutant | melanoma | sensitive | SBI-0640726 | Preclinical | Actionable | In a preclinical study, SBI-0640726 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). | 26603897 |
| NRAS mutant | sarcoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human sarcoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | 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 | lymphoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human lymphoma cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | melanoma | predicted - sensitive | Belvarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Belvarafenib (HM95573) treatment resulted in an unconfirmed partial response in a patient with NRAS mutant melanoma (Journal of Clinical Oncology 34, no. 15_suppl (May 20 2016) 2570-2570; NCT02405065). | detail... |
| NRAS mutant | melanoma | predicted - sensitive | Belvarafenib | Phase I | Actionable | In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in 44% (4/9) of patients with NRAS-mutant melanoma in a dose escalation study, and partial response in 22% (2/9) of NRAS-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). | detail... |
| NRAS mutant | liver cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of liver cancer cell lines harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 |
| NRAS mutant | melanoma | sensitive | 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 | thyroid gland cancer | sensitive | Selumetinib | Phase I | Actionable | In a Phase I study, selumetinib demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine; including patients with BRAF and NRAS mutations disease (PMID: 23406027). | 23406027 |
| NRAS mutant | acute myeloid leukemia | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human acute myeloid leukemia cell lines harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| 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 | 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 | 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 PIK3CA wild-type | colorectal cancer | predicted - sensitive | 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 |
| NRAS mut PIK3CA H1047R | melanoma | predicted - resistant | 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 | 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 + 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 | 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 | 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 | 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 | 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 | 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 |
| NRAS mut TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Pimasertib + SAR405838 | Phase I | Actionable | In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). | 30585255 |
| Molecular Profile | Protein Effect | Treatment Approaches |
|---|---|---|
| NRAS mutant | unknown | |
| BRAF wild-type NRAS mut | ||
| CDKN2A loss NRAS mut | ||
| BRAF mut NRAS mut | ||
| CTNNB1 mut NRAS mut | ||
| NRAS mut PIK3CA wild-type | ||
| NRAS mut PIK3CA H1047R | ||
| NRAS mut PIK3CA E545K | ||
| NRAS Q61L NRAS mut | ||
| NRAS Q61K NRAS mut | ||
| NRAS mut TP53 wild-type |