ArticleMolecular cancer therapeutics2018
Plk1 Inhibition Enhances the Efficacy of BET Epigenetic Reader Blockade in Castration-Resistant Prostate Cancer.
Article in Molecular cancer therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- High-throughput virtual screening, identification andJournal of enzyme inhibition and medicinal chemistry · 2025Article
- Article
- PLK1: A Promising Therapeutic Target for Prostate Cancer Treatment.Serican journal of medicine · 2024Article
- Novel Aminopyrimidine-2,4-diones, 2-Thiopyrimidine-4-ones, and 6-Arylpteridines as Dual-Target Inhibitors of BRD4/PLK1: Design, Synthesis, Cytotoxicity, and Computational Studies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- PROTACs: great opportunities for academia and industry (an update from 2020 to 2021).Signal transduction and targeted therapy · 2022Review
- Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems.Pharmaceutics · 2022Article
- Diptoindonesin G antagonizes AR signaling and enhances the efficacy of antiandrogen therapy in prostate cancer.The Prostate · 2022Article
- Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.Pharmaceutics · 2022Review
- PLK1 inhibition-based combination therapies for cancer management.Translational oncology · 2022Review
- Present and Future Perspective on PLK1 Inhibition in Cancer Treatment.Frontiers in oncology · 2022Review
- A Novel Gene Signature Associated With "E2F Target" Pathway for Predicting the Prognosis of Prostate Cancer.Frontiers in molecular biosciences · 2022Article
- Epigenetics in prostate cancer treatment.Journal of translational genetics and genomics · 2021Article
- Analyses of expressions and prognostic values of Polo-like kinases in non-small cell lung cancer.Journal of cancer research and clinical oncology · 2020Article
- Review
- Small-Molecule Dual PLK1 and BRD4 Inhibitors are Active Against Preclinical Models of Pediatric Solid Tumors.Translational oncology · 2020Article
- Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells.Cancer letters · 2019Article
- The Identification of Potential Biomarkers and Biological Pathways in Prostate Cancer.Journal of Cancer · 2019Article
- Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors.Journal of medicinal chemistry · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Polo-like kinase 1 (Plk1), a crucial regulator of cell-cycle progression, is overexpressed in multiple types of cancers and has been proven to be a potent and promising target for cancer treatment. In case of prostate cancer, we once showed that antineoplastic activity of Plk1 inhibitor is largely due to inhibition of androgen receptor (AR) signaling. However, we also discovered that Plk1 inhibition causes activation of the β-catenin pathway and increased expression of c-MYC, eventually resulting in resistance to Plk1 inhibition. JQ1, a selective small-molecule inhibitor targeting the amino-terminal bromodomains of BRD4, has been shown to dramatically inhibit c-MYC expression and AR signaling, exhibiting antiproliferative effects in a range of cancers. Because c-MYC and AR signaling are essential for prostate cancer initiation and progression, we aim to test whether targeting Plk1 and BRD4 at the same time is an effective approach to treat prostate cancer. Herein, we show that a combination of Plk1 inhibitor GSK461364A and BRD4 inhibitor JQ1 had a strong synergistic effect on castration-resistant prostate cancer (CRPC) cell lines, as well as in CRPC xenograft tumors. Mechanistically, the synergistic effect is likely due to two reasons: (i) Plk1 inhibition results in the accumulation of β-catenin in the nucleus, thus elevation of c-MYC expression, whereas JQ1 treatment directly suppresses c-MYC transcription; (ii) Plk1 and BRD4 dual inhibition acts synergistically in inhibition of AR signaling.
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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 OpenQuestion graph.