Targeting androgen receptor versus targeting androgens to suppress castration resistant prostate cancer.
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941. Multiple strategies related to surgical/chemical castration with combinations of various anti-androgens, including Cyproterone Acetate, Flutamide, Nilutamide, Bicalutamide (Casodex) and Enzalutamide, as well as some androgen synthesis blockers, including Abiraterone, have been used to control PCa progression. However, patients on ADT with anti-androgen treatment eventually develop resistance, which might be accompanied with the unwanted side effects of enhanced metastasis. New therapeutic approaches via directly targeting the AR with ASC-J9®, Cisplatin, EPI-001, Niclosamide, and VPC compounds as well as silencing AR with siRNAs or non-coding RNAs have been developed to further suppress PCa at the castration resistant stages.
Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
Changcheng
C
Guo
Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA.
Shuyuan
S
Yeh
Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology and School of Laboratory Medicine, Tianjin Medical University, Tainjin 300203, China.
Yuanjie
Y
Niu
Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of General Surgery, Chawnshang Chang Liver Cancer Center, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China.
Gonghui
G
Li
Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
Junhua
J
Zheng
Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: lilydr@hotmail.com.
Lei
L
Li
Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Sex Hormone Research Center, China Medical University/Hospital, Taichung 404, Taiwan. Electronic address: chang@urmc.rochester.edu.
Chawnshang
C
Chang
D059002:Androgen Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000009:adverse effects / Q000379:methods*; D011944:Receptors, Androgen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D034741:RNA, Small Interfering; D011944:Receptors, Androgen
AR degradation; AR splicing variant; Anti-androgen; Castration resistant prostate cancer; Combination therapy