ReviewFrontiers in cell and developmental biology2025
Dissecting the MAPK signaling landscape in malignant melanoma: from BRAF and NRAS mutations to precision combination therapies.
Review in Frontiers in cell and developmental biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Therapeutic Resistance in Melanoma: Molecular Mechanisms and Emerging Pharmaceutical Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Integrated Metabolomics, Network Pharmacology, and Molecular Dynamics Simulations Reveal the Potential Anti-Melanoma Mechanisms ofCurrent issues in molecular biology · 2026Article
- Elucidating the molecular mechanisms linking bisphenol A to breast cancer: an integrated study of bioinformatics, machine learning, and molecular docking.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Dynamic ecosystems of tumor drug resistance mechanisms: from molecular heterogeneity to systemic interventions.Apoptosis : an international journal on programmed cell death · 2026Review
Corrections and comments
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Authors and funding
3 authors.
Funding
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Abstract
Malignant melanoma is an aggressive skin malignancy with a complex molecular landscape and limited treatment durability in advanced stages. Aberrations in the MAPK pathway-most notably BRAF and NRAS mutations-have catalyzed the development of targeted therapies, particularly BRAF/MEK inhibitors, which have transformed outcomes in BRAF-mutant melanoma. However, resistance remains prevalent, driven by MAPK reactivation, epigenetic rewiring, and tumor microenvironmental feedback. In NRAS-mutant subtypes, MEK inhibition, CDK4/6 blockade, and immune checkpoint inhibition offer partial efficacy, yet monotherapies fail to achieve sustained responses. Emerging strategies focus on combinatorial regimens targeting RAF-MEK-ERK and PI3K-AKT axes, alongside immunotherapeutic integration. Rarer alterations in KIT and RTKs also define actionable subsets. This review synthesizes recent mechanistic insights and therapeutic advances in mutation-driven melanoma, highlighting the promise of biomarker-guided combination strategies and signaling crosstalk disruption as the next frontier in precision oncology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.