Recent advances on the progressive mechanism and therapy in castration-resistant prostate cancer

Keshan Wang,1 Hailong Ruan,1 Tianbo Xu,1 Lei Liu,1 Di Liu,1 Hongmei Yang,2 Xiaoping Zhang,1 Ke Chen1 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 2Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China Background: Although there have been great advances in mechanisms and therapeutic methods of prostate cancer, the mortality rate of prostate cancer remains high. The castration-resistant prostate cancer (CRPC), which develops from hormone-sensitive prostate cancer, foreshadows a more dismal outcome. Concomitant with the researches in the mechanism of CRPC and therapy for CRPC, more and more landmark progress has been made in recent years. Methods: A number of clinical and experimental studies were reviewed to indicate the novel advancement in the progressive mechanism and therapy of CRPC. Results: The androgen receptor (AR) is still a vital driver in the progression of CRPC, while other multiple mechanisms also contribute to this progression, such as tumor immunity, cancer stem cells, epithelial–mesenchymal transition and DNA repair disorder. In terms of the therapeutic methods of CRPC, chemotherapy with drugs, such as docetaxel, has been the first-line therapy for CRPC for many years. Besides, newer agents, which target some of the above mechanisms, show additional overall survival benefits for CRPC patients. These therapies include drugs targeting the androgen axis pathway (androgen synthesis, androgen receptor splice variants, coactivators of AR and so on), PI3K-AKT pathway, WNT pathway, DNA repair, rearrangement of ETS gene, novel chemotherapy and immunotherapy, bone metastasis therapy and so on. Understanding these novel findings on the mechanisms of CRPC and the latest potential CRPC therapies will direct us for further exploration of CRPC. Conclusion: Through comprehensive consideration, the predominant mechanism of CRPC might be the AR signal axis concomitant with tumor microenvironment, stress, immunity, tumor microenvironment and so on. For CRPC therapy, targeting the AR axis pathway and chemotherapy are the first-line treatments at present. However, with the advancements in CRPC therapy made by the researchers, other novel potential methods will occupy more and more important position in the treatment of CRPC, especially the therapies targeting the tumor microenviroment, tumor immunity and DNA repair and so on. Keywords: CRPC, androgen receptor, tumor immunity, mechanism, therap