Related Experiment Video

Updated: Mar 28, 2026

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

14.2K

Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer

Kavitha Ramachandran1, Carl Speer2, Lubov Nathanson2

  • 1Sylvester Cancer Center, University of Miami, Miami, FL, U.S.A.

Anticancer Research
|January 2, 2016
PubMed
Abstract

Insights

DNA methylation may drive cabazitaxel resistance in prostate cancer. Pre-treating cells with 5-azacytidine restored sensitivity, suggesting a potential therapeutic strategy for metastatic castration-resistant prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Cabazitaxel is a second-line treatment for metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure.
  • Median time to progression on cabazitaxel is limited (2.8 months), indicating acquired resistance.
  • The role of DNA methylation in cabazitaxel resistance remains largely unexplored.

Purpose of the Study:

  • To investigate the potential role of DNA methylation in the development of cabazitaxel resistance.
  • To determine if modulating DNA methylation can overcome cabazitaxel resistance in prostate cancer cells.

Main Methods:

  • Generation of docetaxel- and cabazitaxel-resistant prostate cancer cell lines (DU145 10DRCR).
  • Assessment of cabazitaxel sensitivity following pre-treatment with the DNA methyltransferase inhibitor 5-azacytidine.
  • Gene expression profiling of resistant cells with and without 5-azacytidine treatment.

Main Results:

  • Pre-treatment with 5-azacytidine significantly enhanced sensitivity to cabazitaxel in resistant cells.
  • Gene expression profiling identified specific genes potentially regulated by DNA methylation.
  • These genes are implicated in pro-apoptotic and cell-cycle regulatory pathways.

Conclusions:

  • DNA methylation of key genes likely contributes to cabazitaxel resistance in prostate cancer.
  • Reversing DNA methylation with 5-azacytidine can restore sensitivity to cabazitaxel.
  • This suggests a potential therapeutic approach for overcoming treatment resistance in mCRPC.
Keywords:
DNA methylationEpigeneticsdrug resistanceprostate cancer

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