ArticleJournal of experimental & clinical cancer research : CR2019
Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 100 citations in OpenAlex.
- Beyond conventional therapies: the evolution of targeted agents and immunotherapies in triple-negative breast cancer.Acta pharmacologica Sinica · 2026Review
- Acetylation in ovarian cancer: mechanistic insights into drug resistance and emerging therapeutic opportunities.Journal of ovarian research · 2026Review
- Antibody-bottlebrush prodrug conjugates for targeted cancer therapy.Nature biotechnology · 2026Article
- A LINE-1 retrotransposon promotes SEMA3C expression as a cis-regulatory enhancer to sustain breast cancer stem cell survival.Science China. Life sciences · 2026Article
- Research Progress of PROTACs in Breast Cancer: Subtype-Oriented Target Landscape, Clinical Stratification Evidence, and Engineering Strategies for Translation.Biomedicines · 2026Review
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- Effectiveness of PROTAC BET Degraders in Combating Cisplatin Resistance in Head and Neck Cancer Cells.International journal of molecular sciences · 2025Article
- Androgen-induced AR-BRD4 transcriptional regulatory complex promotes malignant proliferation of osteosarcoma cells.Cell death discovery · 2025Article
- Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancer.Cancer cell international · 2025Article
- Latest Therapeutical Approaches for Triple-Negative Breast Cancer: From Preclinical to Clinical Research.International journal of molecular sciences · 2024Review
- BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression.Oncogene · 2024Article
- Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy.Acta pharmacologica Sinica · 2024Article
- Selective Elimination of Senescent Cancer Cells by Galacto-Modified PROTACs.Journal of medicinal chemistry · 2024Article
- Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer.Molecular cancer · 2024Review
- PROTACs in Ovarian Cancer: Current Advancements and Future Perspectives.International journal of molecular sciences · 2024Review
- Review
- Senolysis Enabled by Senescent Cell-Sensitive Bioorthogonal Tetrazine Ligation.Angewandte Chemie (International ed. in English) · 2024Article
- MZ1, a BRD4 inhibitor, exerted its anti-cancer effects by suppressing SDC1 in glioblastoma.BMC cancer · 2024Article
- Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer.Frontiers in oncology · 2024Review
- Ultrasound Controllable Release of Proteolysis Targeting Chimeras for Triple-Negative Breast Cancer Treatment.Biomaterials research · 2024Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundTriple negative breast cancer (TNBC) is an incurable disease where novel therapeutic strategies are needed. Proteolysis targeting chimeric (PROTAC) are novel compounds that promote protein degradation by binding to an ubiquitin ligase. In this work, we explored the antitumoral activity of two novel BET-PROTACs, MZ1 and ARV-825, in TNBC, ovarian cancer and in a BET inhibitor resistant model.
methodsOVCAR3, SKOV3, BT549, MDA-MB-231 cell lines and the JQ1 resistant cell line MDA-MB-231R were evaluated. MTTs, colony-forming assay, three-dimensional cultures in matrigel, flow cytometry, and western blots were performed to explore the anti-proliferative effect and biochemical mechanism of action of MZ1 and ARV-825. In vivo studies included BALB/c nu/nu mice engrafted with MDA-MB-231R cells.
resultsThe BET-PROTACs MZ1 and ARV-825 efficiently downregulated the protein expression levels of the BET protein BRD4, in MDA-MB-231 and MDA-MB-231R. MZ1 and ARV-825 also showed an antiproliferative effect on sensitive and resistant cells. This effect was corroborated in other triple negative (BT549) and ovarian cancer (SKOV3, OVCAR3) cell lines. MZ1 provoked G2/M arrest in MDA-MB-231. In addition, a profound effect on caspase-dependent apoptosis was observed in both sensitive and resistant cells. No synergistic activity was observed when it was combined with docetaxel, cisplatin or olaparib. Finally, in vivo administration of MZ1 rescued tumor growth in a JQ1-resistant xenograft model, reducing the expression levels of BRD4.
conclusionsUsing both in vitro and in vivo approaches, we describe the profound activity of BET-PROTACs in parental and BETi-resistant TNBC models. This data provides options for further clinical development of these agents in TNBC.
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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 OpenQuestion graph.