BRAF^V600E-PROTAC versus inhibitors in melanoma cells: Deep transcriptomic characterization.

ABSTRACT:

Aims

This study compares the suppression of Mitogen-activated protein kinase (MAPK) signalling and early resistance potential between a proteolysis-targeting chimera (PROTAC) and inhibitors targeting BRAF^V600E.

Methods

We performed a detailed in silico analysis of the transcriptomic landscape of the A375 melanoma cell line treated with a PROTAC and BRAF^V600E inhibitors from RNA sequencing data. The study assessed gene dysregulation, MAPK and Phosphoinositide-3-kinase (PI3K/AKT) pathway inhibition, and cell survival. Key genes uniquely dysregulated by PROTAC treatment were validated by qPCR. Furthermore, analysis was performed to evaluate dedifferentiation and early resistance signatures to understand melanoma drug-induced plasticity.

Results

PROT

SUBMITTER: Alhassan SO 

PROVIDER: S-EPMC11882472 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature