Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects.
Androgen receptor (AR) signaling is a critical pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. However, over time, most tumors become resistant to ADT. The view of castration-resistant prostate cancer (CRPC) has changed dramatically in the last several years. Progress in understanding the disease biology and mechanisms of castration resistance led to significant advancements and to paradigm shift in the treatment. Accumulating evidence showed that prostate cancers develop adaptive mechanisms for maintaining AR signaling to allow for survival and further evolution. The aim of this review is to summarize molecular mechanisms of castration resistance and provide an update in the development of novel agents and strategies to more effectively target the AR signaling pathway.
Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK.
R
R
Ferraldeschi
Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK.
J
J
Welti
Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J
J
Luo
Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK.
G
G
Attard
Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK.
J S
JS
de Bono
D000736:Androstenes / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D004249:DNA Damage / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction
C410798:AR protein, human; D000736:Androstenes; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D010669:Phenylthiohydantoin; C540278:enzalutamide; C089740:abiraterone