NF1 Loss Promotes EGFR Activation and Confers Sensitivity to EGFR Inhibition in NF1-Mutant Melanoma.

ABSTRACT: Targeted therapies and immunotherapy have improved treatment outcomes for many patients with melanoma. However, patients whose melanomas harbor driver mutations in the neurofibromin 1 (NF1) tumor suppressor gene often lack effective targeted treatment options when their tumors do not respond to immunotherapy. In this study, we utilized patient-derived short-term cultures and multiomics approaches to identify molecular features that could inform the development of therapies for patients with NF1-mutant (NF1Mut) melanoma. Differential gene expression analysis revealed that EGFR is highly expressed and active in NF1Mut melanoma cells, in which it hyperactivates ERK and AKT, leading to increased tumor cell proliferation, survival, and growth. In contrast, genetic or pharmacologic inhibition of

SUBMITTER: Ibrahim M 

PROVIDER: S-EPMC12221223 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature