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Updated: Dec 10, 2025

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
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YM155 Reverses Cabazitaxel Resistance in Castration-resistant Prostate Cancer by Reducing Survivin Expression

Takeshi Miyao1, Hidekazu Koike2, Yoshitaka Sekine1

  • 1Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Anticancer Research
|September 4, 2020
PubMed
Abstract

Insights

YM155, a survivin inhibitor, reverses cabazitaxel resistance in castration-resistant prostate cancer (CRPC). This small molecule enhances cabazitaxel

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Castration-resistant prostate cancer (CRPC) often develops resistance to standard chemotherapies like cabazitaxel.
  • Survivin is a protein frequently overexpressed in various cancers, contributing to treatment resistance.
  • YM155 is a novel small-molecule inhibitor targeting survivin.

Purpose of the Study:

  • To investigate if YM155 can overcome cabazitaxel resistance in CRPC.
  • To evaluate the efficacy of YM155 in combination with cabazitaxel against resistant prostate cancer models.

Main Methods:

  • Induction of cabazitaxel resistance in the 22Rv1-CR prostate cancer cell line.
  • In vitro and in vivo studies utilizing 22Rv1-CR cells to assess YM155 and cabazitaxel efficacy.
  • Measurement of survivin gene expression levels.

Main Results:

  • Survivin gene expression was significantly elevated in cabazitaxel-resistant 22Rv1-CR cells compared to parental 22Rv1 cells.
  • YM155 treatment dose-dependently reduced survivin gene expression in 22Rv1-CR cells.
  • While YM155 showed limited efficacy alone, it significantly potentiated the anticancer effects of cabazitaxel both in vitro and in vivo.

Conclusions:

  • Inhibiting survivin with YM155 is a viable strategy to overcome cabazitaxel resistance in CRPC.
  • The combination of YM155 and cabazitaxel demonstrates enhanced therapeutic potential for resistant prostate cancer.
Keywords:
Castration-resistant prostate cancerYM155cabazitaxeldrug therapyinhibitor of apoptosis proteinssurvivin

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