Recent advances in bone-targeted therapies of metastatic prostate cancer

Abstract

Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential therapeutic targets for bone metastases caused by metastatic castration-resistant prostate cancer. In this review, we present the recent advances in molecular targeted therapies for prostate cancer bone metastasis focusing on therapies that target the bone cells and the bone microenvironment. The therapies covered in this review include agents that inhibit bone resorption, agents that stimulate bone formation, and agents that target the bone matrix. Suggestions to devise more effective molecular targeted therapies are proposed. Hopefully, with better understanding of the biology of the disease and the development of more robust targeted therapies, the survival and quality of life of the affected individuals could be significantly improved.

Keywords: Bone metastasis; Molecular targeted therapy; Osteoblasts; Osteoclasts; Prostate cancer; RANKL.

Figure 1. Summary of the agents used to target the bone for prostate cancer metastasis

A schematic overview of the recent development of bone-targeted therapeutic strategies for prostate cancer metastasis that have been investigated in clinical or preclinical studies. A detailed description is provided in the text.