Verma Shiv, Prajapati Kumari Sunita, Kushwaha Prem Prakash, Shuaib Mohd, Kumar Singh Atul, Kumar Shashank, Gupta Sanjay
Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Cancer Drug Resist. 2020 Sep 17;3(4):742-761. doi: 10.20517/cdr.2020.45. eCollection 2020.
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.
针对雄激素/雄激素受体（AR）信号通路的雄激素剥夺疗法仍然是晚期前列腺癌的主要治疗方法。使用第二代抗雄激素药物，如醋酸阿比特龙和恩杂鲁胺，提高了前列腺癌患者的生存率；然而，这些患者中的大多数会进展为去势抵抗性前列腺癌（CRPC）。抗雄激素治疗的耐药机制很复杂，包括特定突变、可变剪接和致癌蛋白扩增，导致各种信号通路失调。在这篇综述中，我们重点关注获得性耐药的主要机制，包括依赖AR和不依赖AR的耐药机制以及导致CRPC出现的其他耐药机制。对AR靶向治疗耐药机制的不断了解将促使人们开展更多研究，以设计出更有效的晚期前列腺癌治疗方法。
