Hormone treatment for prostate cancer: current issues and future directions.
Most prostate cancers are androgen-dependent and essentially respond to androgen ablation therapy. However, these tumors eventually become androgen-independent and progress despite androgen ablation. Since the androgen receptor (AR) sequence was determined, numerous studies have shown that AR plays a critical role in the development of androgen-refractory prostate cancer. Amplification of AR, mutations of AR, and deregulation of growth factors, cytokines and AR co-activators, which could be classified as AR-dependent pathways, are frequently observed in this condition. There are other pathways, AR-independent pathways that bypass AR, which involve neuroendocrine differentiation of prostate cancer cells, deregulation of apoptotic genes and unknown mechanisms related to down-regulation of AR. Androgen-refractory prostate cancers with the AR-dependent pathway could be treated by suppressing AR activity, whereas AR-independent tumors would require alternative management strategies. When more cell survival pathways are defined, improvement of patients' survival could be achieved by developing specific gene-targeting therapies that interfere with those pathways.
Ichikawa
Tomohiko
T
Department of Urology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. tomohiko_ichikawa@faculty.chiba-u.jp
Suzuki
Hiroyoshi
H
Ueda
Takeshi
T
Komiya
Akira
A
Imamoto
Takashi
T
Kojima
Satoko
S
D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000627:therapeutic use*; D004358:Drug Therapy / Q000639:trends; D005544:Forecasting; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D000726:Androgen Antagonists; D000728:Androgens; D011944:Receptors, Androgen