ArticleBritish journal of cancer2020
Targeting BRD/BET proteins inhibits adaptive kinome upregulation and enhances the effects of BRAF/MEK inhibitors in melanoma.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Bridging BET bromodomain and immune checkpoint inhibitors through generative bioorganic frameworks for next-generation cancer immunotherapy.RSC medicinal chemistry · 2026Review
- Article
- Decoding GPCR signaling reprogramming in cancer: molecular mechanisms and therapeutic implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Targeting BRD4-A Promising Therapeutic Option for Glioblastoma?International journal of molecular sciences · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Decoding Bromodomain and Extra-Terminal Domain Protein-Mediated Epigenetic Mechanisms in Human Uterine Fibroids.International journal of molecular sciences · 2025Article
- BET proteins mediate survival mechanisms in human schwannoma model cells challenged with trametinib but not brigatinib.Oncogene · 2025Article
- Elevated NR2F1 underlies the persistence of invasive disease after treatment of BRAF-mutant melanoma.The Journal of clinical investigation · 2025Article
- Functional combinatorial precision medicine for predicting and optimizing soft tissue sarcoma treatments.NPJ precision oncology · 2025Article
- The Killer's Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer.International journal of molecular sciences · 2024Review
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- Targeting Upregulated cIAP2 in SOX10-Deficient Drug Tolerant Melanoma.Molecular cancer therapeutics · 2023Article
- Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression.Experimental & molecular medicine · 2023Article
- Review
- Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment.Cancers · 2021Article
- Small Molecules Targeting HATs, HDACs, and BRDs in Cancer Therapy.Frontiers in oncology · 2020Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBRAF-mutant melanoma patients respond to BRAF inhibitors and MEK inhibitors (BRAFi/MEKi), but drug-tolerant cells persist, which may seed disease progression. Adaptive activation of receptor tyrosine kinases (RTKs) has been associated with melanoma cell drug tolerance following targeted therapy. While co-targeting individual RTKs can enhance the efficacy of BRAFi/MEKi effects, it remains unclear how to broadly target multiple RTKs to achieve more durable tumour growth inhibition.
methodsThe blockage of adaptive RTK responses by the new BET inhibitor (BETi), PLX51107, was measured by RPPA and Western blot. Melanoma growth was evaluated in vitro by colony assay and EdU staining, as well as in skin reconstructs, xenografts and PDX models following BRAFi, MEKi and/or PLX51107 treatment.
resultsTreatment with PLX51107 limited BRAFi/MEKi upregulation of ErbB3 and PDGFR-β expression levels. Similar effects were observed following BRD2/4 depletion. In stage III melanoma patients, expression of BRD2/4 was strongly correlated with ErbB3. PLX51107 enhanced the effects of BRAFi/MEKi on inhibiting melanoma growth in vitro, in human skin reconstructs and in xenografts in vivo. Continuous triple drug combination treatment resulted in significant weight loss in mice, but intermittent BETi combined with continuous BRAFi/MEKi treatment was tolerable and improved durable tumour inhibition outcomes.
conclusionsTogether, our data suggest that intermittent inhibition of BET proteins may improve the duration of responses following BRAFi/MEKi treatment in BRAF-mutant melanoma.
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Registered trials
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