ADT with antiandrogens in prostate cancer induces adverse effect of increasing resistance, neuroendocrine differentiation and tumor metastasis. (28th December 2018)

• Record Type: Journal Article
• Authors: Niu, Yuanjie; Guo, Changcheng; Wen, Simeng; Tian, Jing; Luo, Jie; Wang, Keliang; Tian, Hao; Yeh, Shuyuan; Chang, Chawnshang
• Is Part Of: Cancer letters. Volume 439(2019)
• Page Start: 47
• Page End: 55
• Publication Date: 2018-12-28
• Subjects: Androgen-deprivation-therapy -- Enzalutamide-resistance -- NE differentiation -- Prostate cancer metastasis; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.09.020
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Prostate cancer (PCa) is the most common cancer and the 3rd leading cause of cancer-related deaths among men in the United States. Androgen-deprivation-therapy (ADT) with anti-androgens to target the androgens/androgen receptor (AR) signals remains the standard therapy for advanced PCa. However, most of the PCa patients who received ADT with anti-androgens, including the recently developed Enzalutamide (Enz) that might extend PCa patients survival an extra 4.8 months, will still develop the castration (or anti-androgen) resistance. Mechanism dissection studies suggest these anti-androgen resistances may involve the induction of AR splicing variants and/or AR mutants. Further preclinical in vitro/in vivo studies suggest ADT-anti-androgens may also enhance the neuroendocrine differentiation (NED) and PCa cell invasion, and these unwanted side-effects may function through various mechanisms including altering the infiltrating inflammatory cells within the prostate tumor microenvironment. This review summarizes these unwanted ADT-induced side-effects and discusses multiple approaches to overcome these side-effects to better suppress the PCa at the castration resistant stage. Highlights: The appropriate choice, timing and actual benefits of ADT with anti-androgens in various PCa still remain controversial. ADT treatment has potential side-effects. New therapeutic approaches to overcome these potential side effects to better suppress the PCa at CRPC stage.