BRAF Wild-Type Melanomas with NF1 Mutations: Implications for MEK Inhibitor Therapy in Specific Molecular Subgroups
Year: 2025
Type: article
Abstract: Cutaneous melanoma represents a highly aggressive neoplasm characterized by considerable genomic heterogeneity, with distinct molecular subsets dictating therapeutic responsiveness. While BRAF-mutant melanomas benefit from targeted BRAF/MEK inhibition, BRAF wild-type (BRAF WT) tumors lacking NRAS mutations present a therapeutic challenge, particularly those harboring neurofibromin 1 (NF1) loss-of-function alterations. This article explores the molecular landscape of NF1-mutated, BRAF WT melanomas, emphasizing the potential role of constitutive MAPK pathway activation via RAS-RAF-MEK-ERK signaling dysregulation. Emerging evidence suggests that MEK inhibitors (MEKi) may exhibit clinical efficacy in this subset, though response heterogeneity underscores the need for refined patient stratification. We discuss the mechanistic rationale for MEK inhibition in NF1-deficient melanomas, addressing predictive biomarkers, resistance mechanisms, and combinatorial strategies to optimize therapeutic outcomes in this genomically defined cohort.
Authors: Lizeth Montelongo Cedillo, Jorge Daniel Velázquez López, Universidad Nacional Autónoma de México. Ciudad Universitaria. México., Emanuel Chew Bonilla, Universidad Autónoma del Estado de México. Mexico., Roberto Hernández Hernández, Escuela Nacional de Medicina y Homeopatía Instituto Politécnico Nacional. México., Sánchez Gómez Jessica, Escuela Superior de Medicina. Instituto Politécnico Nacional. Mexico
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4414447963
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