Xu Lingfan, Chen Junyi, Liu Weipeng, Liang Chaozhao, Hu Hailiang, Huang Jiaoti
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Pathology, Duke University School of Medicine, Durham, NC, USA.
Asian J Urol. 2019 Jan;6(1):91-98. doi: 10.1016/j.ajur.2018.11.002. Epub 2018 Nov 28.
Since androgen receptor (AR) signaling is critically required for the development of prostate cancer (PCa), targeting AR axis has been the standard treatment of choice for advanced and metastatic PCa. Unfortunately, although the tumor initially responds to the therapy, treatment resistance eventually develops and the disease will progress. It is therefore imperative to identify the mechanisms of therapeutic resistance and novel molecular targets that are independent of AR signaling. Recent advances in pathology, molecular biology, genetics and genomics research have revealed novel AR-independent pathways that contribute to PCa carcinogenesis and progression. They include neuroendocrine differentiation, cell metabolism, DNA damage repair pathways and immune-mediated mechanisms. The development of novel agents targeting the non-AR mechanisms holds great promise to treat PCa that does not respond to AR-targeted therapies.
由于雄激素受体（AR）信号传导对于前列腺癌（PCa）的发展至关重要，靶向AR轴一直是晚期和转移性PCa的标准治疗选择。不幸的是，尽管肿瘤最初对治疗有反应，但最终会产生治疗抗性，疾病会进展。因此，必须确定治疗抗性的机制以及独立于AR信号传导的新型分子靶点。病理学、分子生物学、遗传学和基因组学研究的最新进展揭示了有助于PCa致癌和进展的新型AR非依赖性途径。它们包括神经内分泌分化、细胞代谢、DNA损伤修复途径和免疫介导机制。靶向非AR机制的新型药物的开发有望治疗对AR靶向治疗无反应的PCa。
