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Adapting to hormone-therapy resistance for adopting the right therapeutic strategy in advanced prostate cancer

Giacomo Nuvola1, Matteo Santoni2, Mimma Rizzo3

  • 1Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.

Expert Review of Anticancer Therapy
|May 15, 2023
PubMed
Abstract

Insights

Understanding resistance to hormone therapy (HT) in prostate cancer (PCa) is crucial. This review details androgen receptor (AR) dependent and independent mechanisms driving treatment failure in PCa.

Area of Science:

  • Oncology
  • Molecular Biology
  • Urology

Background:

  • The androgen/androgen receptor (AR) axis is central to prostate cancer (PCa) progression and a primary cause of treatment resistance.
  • Androgen deprivation therapy (ADT) and targeted agents are standard treatments, but resistance limits their efficacy.

Approach:

  • This review synthesizes current data and emerging evidence on resistance mechanisms to hormone therapy (HT) in PCa.
  • Focus is placed on both primary and secondary resistance pathways.

Key Points:

  • Resistance mechanisms include AR gene amplification, somatic AR mutations, and intratumoral androgen synthesis.
  • Both AR-dependent and AR-independent pathways contribute to treatment failure.
  • Novel therapeutic strategies are required to overcome resistance.

Conclusions:

  • A comprehensive understanding of resistance mechanisms is fundamental for developing effective therapeutic strategies.
  • Personalized anticancer therapies are needed to improve outcomes for patients with HT-resistant PCa.
Keywords:
Abiraterone acetateandrogen receptordrug resistanceenzalutamidehormone therapymetastatic prostate cancerneuroendocrine transformation

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