Role of the Androgen-Androgen Receptor Axis in the Treatment Resistance of Advanced Prostate Cancer: From Androgen-Dependent to Castration Resistant and Further

DOI IR Web Site Web Site Web Site View 1 Remaining Hide 1 Citations 56 References
  • FUJIMOTO Naohiro
    Department of Urology, School of Medicine, University of Occupational and Environmental Health, Japan

Bibliographic Information

Other Title
  • 前立腺癌進展におけるアンドロゲン-アンドロゲン受容体の役割

Search this article

Abstract

After the introduction of prostate-specific antigen (PSA) screening, prostate cancer diagnosis has shifted to early and curative stages, although 10-20% of patients still present with metastatic and incurable cancer. Prostate cancer is androgen-dependent, and most patients with prostate cancer initially respond to androgen deprivation therapy (ADT). After 1-2 years of the treatment, advanced prostate cancer eventually progresses to castration resistant prostate cancer (CRPC). A variety of mechanisms of progression from androgen-dependent prostate cancer to CRPC under ADT have been postulated, and the key pathway is re-activation of the androgen-androgen receptor (AR) axis, for example, caused by AR mutation/overexpression/splice variants, altered expression of AR cofactors, and increased production of androgens. Recently approved new agents, such as the hormonal agents abiraterone and enzalutamide and the chemotherapeutic agent cabazitaxel, have demonstrated survival benefit in men with CRPC. However, the prolongation of survival times provided with these agents is limited because of the treatment resistance. Androgen-AR axis still plays a pivotal role in the resistance to the new agents for CRPC. To improve the prognosis of patients with CRPC, intensive research to identify effective agents, treatment strategies, and useful predictive biomarkers to select the patients who can benefit from such treatments are required. Additional clinical data, with a better understanding of the biology of CRPC, may provide better CRPC treatment outcomes. This article reviews the underlying mechanisms of treatment resistance and future direction of CRPC treatments.

Journal

  • Journal of UOEH

    Journal of UOEH 38 (2), 129-138, 2016

    The University of Occupational and Environmental Health, Japan

Citations (1)*help

See more

References(56)*help

See more

Keywords

Report a problem

Back to top