Dynamic transcriptome analysis reveals signatures of paradoxical effect of vemurafenib on human dermal fibroblasts.

ABSTRACT:

Background

Vemurafenib (PLX4032) is one of the most frequently used treatments for late-stage melanoma patients with the BRAF^V600E mutation; however, acquired resistance to the drug poses as a major challenge. It remains to be determined whether off-target effects of vemurafenib on normal stroma components could reshape the tumor microenvironment in a way that contributes to cancer progression and drug resistance.

Methods

By using temporally-resolved RNA- and ATAC-seq, we studied the early molecular changes induced by vemurafenib in human dermal fibroblast (HDF), a main stromal component in melanoma and other tumors with high prevalence of BRAF^V600 mutations.

Results

Transcriptomics analyses revealed a stepwise up-regulation of proliferation sign

SUBMITTER: Corrales E 

PROVIDER: S-EPMC8686565 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature