Fujimoto Naohiro
   Department   School of Medicine  Urology, Clinical Medical Sciences
Article types review
Language English
Peer review Peer reviewed
Presence of invitation Invited paper
Title Role of the Androgen-Androgen Receptor Axis in the Treatment Resistance of Advanced Prostate Cancer: From Androgen-Dependent to Castration Resistant and Further.
Journal Formal name:Journal of UOEH
Abbreviation:J UOEH
ISSN code:0387821X/0387821X
Domestic / ForeginDomestic
Volume, Issue, Page 38(2),129-38頁
Author and coauthor Fujimoto Naohiro
Publication date 2016/06
Summary 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.
DOI 10.7888/juoeh.38.129
PMID 27302726