Targeting tumor and bone microenvironment: Novel therapeutic opportunities for castration-resistant prostate cancer patients with bone metastasis

Despite standard hormonal therapy that targets the androgen receptor (AR) attenuates prostate cancer (PCa) effectively in the initial stage, the tumor ultimately converts to castration-resistant prostate cancer (CRPC), and the acquired resistance is still a great challenge for the management of advanced prostate cancer patients. The tumor microenvironment (TME) consists of multiple cellular and noncellular agents is well known as a vital role during the development and progression of CRPC by establishing communication between TME and tumor cells. Additionally, as primary prostate cancer progresses towards metastasis, and CRPC always experiences bone metastasis, the TME is conducive to the spread of tumors to the distant sits, particularly in bone. In addition, the bone microenvironment (BME) is also closely related to the survival, growth and colonization of metastatic tumor cells. The present review summarized the recent studies which mainly focused on the role of TME or BME in the CRPC patients with bone metastasis, and discussed the underlying mechanisms, as well as the potential therapeutic values of targeting TME and BME in the management of metastatic CRPC patients.