ArticleMolecular cancer2014
MEK targeting in N-RAS mutated metastatic melanoma.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
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- Antitumor Activity of Metformin in Combination with Binimetinib Against Melanoma Cells.International journal of molecular sciences · 2025Article
- Combination of the Novel RAF Dimer Inhibitor Brimarafenib With the MEK Inhibitor Mirdametinib Is Effective Against NRAS Mutant Melanoma.Pigment cell & melanoma research · 2025Article
- Targeting BRAF Class II and III Mutations in NSCLC with the pan-RAF inhibitor Exarafenib Reveals ARAF-KSR1-Mediated Resistance and Rational Combination Strategies.Research square · 2025Article
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- Targeted DNA Sequencing of Cutaneous Melanoma Identifies Prognostic and Predictive Alterations.Cancers · 2024Article
- Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments antitumor activity in melanoma.JCI insight · 2023Article
- MicroRNA in adenoid cystic carcinoma (Review).International journal of oncology · 2023Review
- Reovirus infection of tumor cells reduces the expression of NKG2D ligands, leading to impaired NK-cell cytotoxicity and functionality.Frontiers in immunology · 2023Article
- Melanogenesis and the Targeted Therapy of Melanoma.Biomolecules · 2022Review
- Clinical significance and immune landscape of KIR2DL4 and the senescence-based signature in cutaneous melanoma.Cancer science · 2022Article
- Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation.Signal transduction and targeted therapy · 2022Article
- Clinical Translation of Combined MAPK and Autophagy Inhibition inInternational journal of molecular sciences · 2021Review
- Epidemiology of brain metastases and leptomeningeal disease.Neuro-oncology · 2021Review
- Unraveling the Wide Spectrum of Melanoma Biomarkers.Diagnostics (Basel, Switzerland) · 2021Review
- Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy.Cell reports · 2021Article
- Current Perspectives and Novel Strategies ofOncoTargets and therapy · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGain of function mutations in B-RAF and N-RAS occur frequently in melanoma, leading to mitogen activating protein kinase (MAPK) pathway activation, and this pathway is the target of drugs in development. Our purpose was to study clinical characteristics of patients with mutations in this pathway and to determine activity of inhibitors of B-RAF and MEK in short term cultures grown from tumors of some of these patients.
methodsClinical and pathologic data were collected retrospectively on melanoma patients tested for B-RAF and N-RAS mutations at the Yale Cancer Center and associations with survival were determined. We studied in vitro activity of the pan-RAF inhibitor, RAF265, and the MEK inhibitor, MEK162, in 22 melanoma short term cultures. We further characterized the effect of MEK inhibition on apoptosis and growth of melanoma cultures.
resultsIn a cohort of 144 metastatic melanoma patients we found that patients with N-RAS mutant melanoma had a worse prognosis. These patients were more likely to have brain metastases at the time of presentation with metastatic disease than their N-RAS-wild-type counterparts. All N-RAS mutant melanoma cultures tested in our study (n = 7) were sensitive to MEK inhibition 162. Exposure to MEK162 reduced ERK1/2 phosphorylation, and induced apoptosis. Clonogenic survival was significantly reduced in sensitive melanoma cell cultures.
conclusionsThe prognosis of patients with melanoma expressing constitutively active N-RAS is poor, consistent with studies performed at other institutions. N-RAS mutant melanoma cultures appear to be particularly sensitive to MEK162, supporting ongoing clinical trials with MEK162 in N-RAS mutated melanoma.
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