摘要
Androgen deprivation therapy targeting the androgens/androgen receptor(AR)signaling continues to be the mainstay treatment of advanced-stage prostate cancer.The use of second-generation antiandrogens,such as abiraterone acetate and enzalutamide,has improved the survival of prostate cancer patients;however,a majority of these patients progress to castration-resistant prostate cancer(CRPC).The mechanisms of resistance to antiandrogen treatments are complex,including specific mutations,alternative splicing,and amplification of oncogenic proteins resulting in dysregulation of various signaling pathways.In this review,we focus on the major mechanisms of acquired resistance to second generation antiandrogens,including AR-dependent and AR-independent resistance mechanisms as well as other resistance mechanisms leading to CRPC emergence.Evolving knowledge of resistance mechanisms to AR targeted treatments will lead to additional research on designing more effective therapies for advanced-stage prostate cancer.
基金
Efforts are supported by the Department of Defense Grant(W81XWH-18-1-0618 and W81XWH-19-1-0720)to Gupta S.Kushwaha PP acknowledges financial support from University Grants Commission,India in the form of CSIR-UGC Senior Research fellowship
Kumar S acknowledges University Grants Commission,India
Department of Science and Technology,India for providing financial support in the form of UGC-BSR Research Start-Up-Grant[F.30-372/2017(BSR)]
DST-SERB Grant(EEQ/2016/000350)respectively.Kumar S acknowledges Central University of Punjab,Bathinda,India for providing Research Seed Money Grant(GP-25)
Singh AK,Prajapati KS,and Shuaib M acknowledge CSIR-India,DBT-India and DST-India funding agencies respectively for providing financial assistance in the form of Junior Research Fellowship.
