ArticleMolecular cancer2015
Combination of pan-RAF and MEK inhibitors in NRAS mutant melanoma.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- Efficacy and safety of regorafenib in patients with advanced pretreated melanoma: results of the RegoMel phase II clinical trial.ESMO open · 2026Trial
- Assessment of pharmacodynamic interactions of two-drug combinations of five selected cytostatics in an in vitro model of human melanoma: an isobolographic analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Combination of the Novel RAF Dimer Inhibitor Brimarafenib With the MEK Inhibitor Mirdametinib Is Effective Against NRAS Mutant Melanoma.Pigment cell & melanoma research · 2025Article
- Single-cell transcriptome analysis suggests cells of the tumor microenvironment as a major discriminator between brain and extracranial melanoma metastases.Biology direct · 2025Article
- Capacity for Compensatory Cyclin D2 Response Confers Trametinib Resistance in Canine Mucosal Melanoma.Cancers · 2025Article
- Capacity for compensatory cyclin D2 response confers trametinib resistance in canine mucosal melanoma.bioRxiv : the preprint server for biology · 2025Article
- Article
- Dissecting the MAPK signaling landscape in malignant melanoma: from BRAF and NRAS mutations to precision combination therapies.Frontiers in cell and developmental biology · 2025Review
- Regorafenib Combined with BRAF/MEK Inhibitors for the Treatment of Refractory Melanoma Brain Metastases.Cancers · 2024Article
- Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling.International journal of cancer · 2024Article
- Article
- Revisiting the Role of B-RAF Kinase as a Therapeutic Target in Melanoma.Current medicinal chemistry · 2024Article
- Exploring the In Vitro and In Vivo Therapeutic Potential of BRAF and MEK Inhibitor Combination in NRAS-Mutated Melanoma.Cancers · 2023Article
- TargetingJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Melanogenesis and the Targeted Therapy of Melanoma.Biomolecules · 2022Review
- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Immune Checkpoint Inhibitors and RAS-ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma.Biomolecules · 2022Review
- SFPQ promotes RAS-mutant cancer cell growth by modulating 5'-UTR mediated translational control of CK1α.NAR cancer · 2022Article
- Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies.Cancers · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundApproximately 20% of melanomas contain a mutation in NRAS. However no direct inhibitor of NRAS is available. One of the main signaling pathways downstream of NRAS is the MAPK pathway. In this study we investigated the possibility of blocking oncogenic signaling of NRAS by inhibiting two signaling points in the MAPK pathway.
methodsFourteen NRAS mutated human melanoma cell lines were treated with a pan-RAF inhibitor (PRi, Amgen Compd A), a MEK inhibitor (MEKi, trametinib) or their combination and the effects on proliferation, cell cycle progression, apoptosis, transcription profile and signaling of the cells were investigated.
resultsThe majority of the cell lines showed a significant growth inhibition, with high levels of synergism of the PRi and MEKi combination. Sensitive cell lines showed induction of apoptosis by the combination treatment and there was a correlation between p-MEK levels and synergistic effect of the combination treatment. Proliferation of sensitive cell lines was blocked by the inhibition of the MAPK pathway, which also blocked expression of cyclin D1. However, in resistant cell lines, proliferation was blocked by combined inhibition of the MAPK pathway and cyclin D3, which is not regulated by the MAPK pathway. Resistant cell lines also showed higher levels of p-GSK3β and less perturbation of the apoptotic profile upon the treatment in comparison with the sensitive cell lines.
conclusionsThe combination of PRi + MEKi can be an effective regimen for blocking proliferation of NRAS mutant melanomas when there is higher activity of the MAPK pathway and dependence of proliferation and survival on this pathway.
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