ArticleLife science alliance2024
Off-targets of BRAF inhibitors disrupt endothelial signaling and vascular barrier function.
Article in Life science alliance, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed.
- Decellularized Dermis ECM-Based Melanoma-on-a-Chip Model with Integrated Lymphatic and Vascular Networks for High-Throughput Drug Testing.ACS applied bio materials · 2026Article
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- The risk of radiation necrosis from combined radiotherapy and BRAF inhibitor in lung adenocarcinoma brain metastases: a comprehensive review and future perspectives.Frontiers in oncology · 2026Review
- Increased Mitochondrial Superoxide Level Is Partially Associated With Vemurafenib-Induced Renal Tubular Toxicity.Basic & clinical pharmacology & toxicology · 2025Article
- Drug repurposing candidates for amyotrophic lateral sclerosis using common and rare genetic variants.Brain communications · 2025Article
- BRAF Modulates the Interplay Between Cell-Cell and Cell-Extracellular Matrix Adhesions in PECAM-1-Mediated Mechanotransduction.International journal of molecular sciences · 2024Article
- The evolution of BRAF-targeted therapies in melanoma: overcoming hurdles and unleashing novel strategies.Frontiers in oncology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted therapies against mutant BRAF are effectively used in combination with MEK inhibitors (MEKi) to treat advanced melanoma. However, treatment success is affected by resistance and adverse events (AEs). Approved BRAF inhibitors (BRAFi) show high levels of target promiscuity, which can contribute to these effects. The blood vessel lining is in direct contact with high plasma concentrations of BRAFi, but effects of the inhibitors in this cell type are unknown. Hence, we aimed to characterize responses to approved BRAFi for melanoma in the vascular endothelium. We showed that clinically approved BRAFi induced a paradoxical activation of endothelial MAPK signaling. Moreover, phosphoproteomics revealed distinct sets of off-targets per inhibitor. Endothelial barrier function and junction integrity were impaired upon treatment with vemurafenib and the next-generation dimerization inhibitor PLX8394, but not with dabrafenib or encorafenib. Together, these findings provide insights into the surprisingly distinct side effects of BRAFi on endothelial signaling and functionality. Better understanding of off-target effects could help to identify molecular mechanisms behind AEs and guide the continued development of therapies for BRAF-mutant melanoma.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.