Metabolic crosstalk in the metastatic prostate cancer-bone microenvironment: mechanism, detection and therapeutic strategies.

Androgen deprivation therapy is the main treatment for prostate cancer (PCa). However, the majority of cases will advance to castration-resistant prostate cancer (CRPC) and then to metastatic CRPC (mCRPC), with bone metastasis accounting for over 90% of mCRPC cases. PCa bone metastasis appears predominantly osteosclerotic, and the processes of bone formation and bone resorption are dysregulated in the presence of PCa. It has been highlighted that cancer cells can adjust their metabolism selectively and dynamically at each stage of the metastatic cascade. More evidence has shown that metabolic reprogramming in the tumor-bone microenvironment plays a key role in promoting disease progression. Therefore, understanding the complex process between bone metastasis and metabolism in PCa could uncover novel targets to tackle these difficult questions in cancer. This review aims to present the latest discovery in the metabolic shifts (including glucose, lipid, and amino acid metabolism) in the bone microenvironment and the crosstalk between PCa cells and the bone local resident cells (such as adipocytes, osteoblasts, osteoclasts, and immune cells). The metabolism-associated and bone-targeted therapeutic strategies and biomarkers are also explored.