ArticleProstate cancer and prostatic diseases2023
Discovery of a new candidate drug to overcome cabazitaxel-resistant gene signature in castration-resistant prostate cancer by in silico screening.
Article in Prostate cancer and prostatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Effect of TGF-β mediated phenotypic changes on prostate cancer cell anoikis response.Oncogene · 2025Article
- Omics-Mediated Treatment for Advanced Prostate Cancer: Moving Towards Precision Oncology.International journal of molecular sciences · 2025Review
- In silico exploration of anti-prostate cancer compounds from differential expressed genes.BMC urology · 2024Article
- Computer-aided drug discovery strategies for novel therapeutics for prostate cancer leveraging next-generating sequencing data.Expert opinion on drug discovery · 2024Review
- G-protein signaling of oxytocin receptor as a potential target for cabazitaxel-resistant prostate cancer.PNAS nexus · 2024Article
- Inhibition of the serine/threonine kinase BUB1 reverses taxane resistance in prostate cancer.iScience · 2023Article
- Review
- A hitchhiker's guide to cancer models.Trends in biotechnology · 2022Review
- Preclinical and Clinical Research Models of Prostate Cancer: A Brief Overview.Life (Basel, Switzerland) · 2022Review
- Repurposing Antipsychotics for Cancer Treatment.Biomedicines · 2021Review
- Topoisomerase II alpha inhibition can overcome taxane-resistant prostate cancer through DNA repair pathways.Scientific reports · 2021Article
- Effects of miR-103a-3p Targeted Regulation of TRIM66 Axis on Docetaxel Resistance and Glycolysis in Prostate Cancer Cells.Frontiers in genetics · 2021Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe taxane cabazitaxel (CBZ) is a promising treatment for docetaxel-resistant castration-resistant prostate cancer (CRPC). However, the survival benefit with CBZ for patients with CRPC is limited. This study used screening tests for candidate drugs targeting CBZ-resistant-related gene expression and identified pimozide as a potential candidate for overcoming CBZ resistance in CRPC.
methodsWe established CBZ-resistant cell lines, DU145CR and PC3CR by incubating DU145 cells and PC3 cells with gradually increasing concentrations of CBZ. We performed in silico drug screening for candidate drugs that could reprogram the gene expression signature of a CBZ-resistant prostate cancer cells using a Connectivity Map. The in vivo effect of the drug combination was tested in xenograft mice models.
resultsWe identified pimozide as a promising candidate drug for CBZ-resistant CRPC. Pimozide had a significant antitumor effect on DU145CR cells. Moreover, combination treatment with pimozide and CBZ had a synergic effect for DU145CR cells in vitro and in vivo. Microarray analysis identified AURKB and KIF20A as potential targets of pimozide in CBZ-resistant CRPC. DU145CR had significantly higher AURKB and KIF20A expression compared with a non-CBZ-resistant cell line. Inhibition of AURKB and KIF20A had an antitumor effect in DU145CR xenograft tumors. Higher expression of AURKB and KIF20A was a poor prognostic factor of TGCA prostate cancer cohort. CBZ-resistant prostate cancer tissues in our institution had higher AURKB and KIF20A expression.
conclusionsPimozide appears to be a promising drug to overcome CBZ resistance in CRPC by targeting AURKB and KIF20A.
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