PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer

作     者：Ling-Yu Wang Chiu-Lien Hung Tsan-Chun Wang Hung-Chih Hsu Hsing-Jien Kung Kwang-Huei Lin 

作者机构：1Department of Biochemistry and Molecular Biology Chang Gung University Taoyuan Taiwan email: lywang@mail.cgu.edu.tw 2Division of Hematology-Oncology Chang Gung Memorial Hospital at Linkou Taoyuan Taiwan 3Graduate Institute of Biomedical Sciences College of Medicine Chang Gung University Taoyuan Taiwan 4Department of Preclinical Drug Discovery Technology Biomedical Technology and Devices Research Labs Industrial Technology Research Institute Hsinchu Taiwan 5College of Medicine Chang Gung University Taoyuan Taiwan 6Research Center of Cancer Translational Medicine and PhD Program for Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan 7Liver Research Center Chang Gung Memorial Hospital Linkou Taoyuan Taiwan 8Research Center for Chinese Herbal Medicine College of Human Ecology Chang Gung University of Science and Technology Taoyuan Taiwan 

出 版 物：《Organizational Psychology and Organizational Behavior》 

年 卷 期：1000年第12卷第1期

页      面：375-396页

摘      要：Castration-resistant prostate cancer (CRPC) presents significant challenges in clinical management due to its resistance to conventional androgen receptor (AR)-targeting therapies. The advent of proteolysis targeting chimeras (PROTACs) has revolutionized cancer therapy by enabling the targeted degradation of key molecular players implicated in CRPC progression. In this review we discuss the developments of PROTACs for CRPC treatment, focusing on AR and other CRPC-associated regulators. We provide an overview of the strategic trends in AR PROTAC development from the aspect of targeting site selection and preclinical antitumor evaluation, as well as updates on AR degraders in clinical applications. Additionally, we briefly address the current status of selective AR degrader development. Furthermore, we review new developments in PROTACs as potential CRPC treatment paradigms, highlighting those targeting chromatin modulators BRD4, EZH2, and SWI/SNF; transcription regulator SMAD3; and kinases CDK9 and PIM1. Given the molecular targets shared between CRPC and neuroendocrine prostate cancer (NEPC), we also discuss the potential of PROTACs in addressing NEPC.