Androgen Receptor Signaling in the Development of Castration-Resistant Prostate Cancer

Qin Feng, Bin He

Research output: Contribution to journalReview article

17 Scopus citations

Abstract

Most prostate cancers are androgen-sensitive malignancies whose growths depend on the transcriptional activity of the androgen receptor (AR). In the 1940s, Charles Huggins demonstrated that the surgical removal of testes in men can result in a dramatic improvement in symptoms and can induce prostate cancer regression. Since then, androgen deprivation therapies have been the standard first-line treatment for advanced prostate cancer, including: surgical castration, medical castration, antiandrogens, and androgen biosynthesis inhibitors. These therapies relieve symptoms, reduce tumor burden, and prolong patient survival, while having relatively modest side effects. Unfortunately, hormone deprivation therapy rarely cures the cancer itself. Prostate cancer almost always recurs, resulting in deadly castration-resistant prostate cancer. The underlying escape mechanisms include androgen receptor gene/enhancer amplification, androgen receptor mutations, androgen receptor variants, coactivator overexpression, intratumoral de novo androgen synthesis, etc. Whereas, the majority of the castration-resistant prostate cancers continuously rely on the androgen axis, a subset of recurrent cancers have completely lost androgen receptor expression, undergone divergent clonal evolution or de-differentiation, and become truly androgen receptor-independent small-cell prostate cancers. There is an urgent need for the development of novel targeted and immune therapies for this subtype of prostate cancer, when more deadly small-cell prostate cancers are induced by thorough androgen deprivation and androgen receptor ablation.

Original languageEnglish (US)
Article number858
JournalFrontiers in Oncology
Volume9
DOIs
StatePublished - Sep 4 2019

Keywords

  • androgen deprivation therapy (ADT)
  • androgen receptor (AR)
  • antiandrogen
  • castration-resistant prostate cancer (CRPC)
  • prostate cancer (PCa)
  • small-cell prostate cancer (SCPC)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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