Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications

Gaetano Aurilio, Alessia Cimadamore, Roberta Mazzucchelli, Antonio Lopez-Beltran, Elena Verri, Marina Scarpelli, Francesco Massari, Liang Cheng, Matteo Santoni, Rodolfo Montironi

Research output: Contribution to journalReview articlepeer-review

Abstract

Around 80-90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient's response to androgen ablation therapy is variable, and 20-30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs.

Original languageEnglish
JournalCells
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 10 2020

Keywords

  • androgen receptor
  • AR antagonists
  • AR resistance
  • AR variants
  • AR-V7
  • prostate cancer

ASJC Scopus subject areas

  • Medicine(all)

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