Targeting androgen receptor-independent pathways in therapy-resistant prostate cancer.

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.

Asian journal of urology. 2018 Nov 28 [Epub]

Lingfan Xu, Junyi Chen, Weipeng Liu, Chaozhao Liang, Hailiang Hu, Jiaoti Huang

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China., Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China., Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China., Department of Pathology, Duke University School of Medicine, Durham, NC, USA.