ArticleCell communication and signaling : CCS2021
Dynamic transcriptome analysis reveals signatures of paradoxical effect of vemurafenib on human dermal fibroblasts.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- New hybrid pyridine-1,2,4-triazole scaffolds: synthesis, in vitro evaluation of anticancer and antimicrobial activity, and in silico insights.Scientific reports · 2026Article
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- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- Chromosome 3p deletion leads to extensive genomic alterations in diverse cancers and confers synthetic lethality in uveal melanoma.bioRxiv : the preprint server for biology · 2026Article
- Suppression of Sebum Production by Vemurafenib Through Paradoxical ERK Activation Resulted in the Inhibition of the mTOR Pathway in 5α-Dihydrotestosterone-Differentiated Hamster Sebocytes In Vitro.Experimental dermatology · 2025Article
- Off-targets of BRAF inhibitors disrupt endothelial signaling and vascular barrier function.Life science alliance · 2024Article
- PI3K/AKT signaling allows for MAPK/ERK pathway independency mediating dedifferentiation-driven treatment resistance in melanoma.Cell communication and signaling : CCS · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundVemurafenib (PLX4032) is one of the most frequently used treatments for late-stage melanoma patients with the BRAF
methodsBy 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
resultsTranscriptomics analyses revealed a stepwise up-regulation of proliferation signatures, together with a down-regulation of autophagy and proteolytic processes. The gene expression changes in HDF strongly correlated in an inverse way with those in BRAF
conclusionsVemurafenib induces paradoxical changes in HDF, enabled by a permissive chromatin landscape. These changes might provide an advantage during combination therapies, by compensating for the toxicity induced in stromal cells by less specific MAPK/ERK inhibitors. Our results highlight the relevance of evaluating the effects of the drugs on non-transformed stromal components, carefully considering the implications of their administration either as mono- or combination therapies. Video Abstract.
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