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Updated: Feb 13, 2026

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

Published on: September 8, 2017

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Profiling Prostate Cancer Therapeutic Resistance

Cameron A Wade1, Natasha Kyprianou2,3,4

  • 1Departments of Urology, University of Kentucky College of Medicine, Lexington, Kentucky, KY 40536, USA. cameron.wade@uky.edu.

International Journal of Molecular Sciences
|March 23, 2018
PubMed

Insights

Therapeutic resistance in advanced prostate cancer is driven by the tumor microenvironment and epithelial-mesenchymal transition (EMT). Targeting EMT-MET dynamics offers a new strategy to overcome treatment resistance in metastatic castration-resistant prostate cancer (mCRPC).

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Therapeutics

Background:

  • Advanced lethal prostate cancer often develops resistance to androgen-deprivation therapy (ADT) and chemotherapy.
  • Therapeutic resistance is influenced by the tumor microenvironment, not solely androgen receptor (AR) signaling.
  • Epithelial-mesenchymal transition (EMT), driven by transforming growth factor-β (TGF-β), promotes cancer cell survival, invasion, and stem cell properties via anoikis resistance.

Purpose of the Study:

  • To review recent evidence on targeting the dynamic interconversions between EMT and mesenchymal-epithelial transition (MET) to overcome therapeutic resistance in prostate cancer.
  • To explore the role of the tumor microenvironment and phenotypic plasticity in conferring treatment resistance.
  • To identify potential new drug targets and therapeutic strategies for advanced, treatment-resistant prostate cancer.

Main Methods:

  • Review of current scientific literature focusing on EMT, MET, anoikis, and the tumor microenvironment in prostate cancer.
  • Analysis of signaling pathways involved in therapeutic resistance, including AR and TGF-β.
  • Discussion of potential therapeutic interventions targeting EMT-MET dynamics and associated biomarkers.

Main Results:

  • EMT facilitates resistance to anoikis, promoting metastasis and chemoresistance through mechanisms like E-cadherin loss.
  • The plasticity of prostate tumor epithelium allows for EMT and MET, contributing to tumor progression and treatment resistance.
  • The lead agent DZ-50 shows potential efficacy in metastatic castration-resistant prostate cancer (mCRPC) by inducing an anoikis-driven therapeutic response.

Conclusions:

  • Targeting the EMT-MET dynamic is a promising strategy to overcome therapeutic resistance in advanced prostate cancer.
  • Understanding the tumor microenvironment's role is crucial for developing effective treatments for resistant prostate cancer.
  • Further research into targeting androgen/AR and TGF-β signaling interactions may optimize therapeutic regimens for mCRPC.
Keywords:
androgen receptorepithelial plasticitymetabolic changestumor landscape

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