Recent developments in treatments targeting castration-resistant prostate cancer bone metastases.

BACKGROUND Prostate cancer is the most common male cancer and one of the top causes of male cancer-related death. Most patients with prostate cancer respond to initial androgen deprivation therapy before progressing to castration-resistant prostate cancer (CRPC) and eventually developing bone metastases. Growth of prostate cancer metastases in the bone microenvironment produces numerous factors that disrupt the dynamic equilibrium of osteogenesis and osteolysis existing in healthy bone, leading to progressive morbidity, poor quality of life, and increased treatment costs. MATERIALS AND METHODS Relevant studies of CRPC and targeted therapies were identified from literature and clinical trial databases, websites, and conference abstracts. RESULTS Available data on agents potentially targeting bone metastatic CRPC or the bone microenvironment in patients with CRPC are discussed, including inhibitors of tumor growth/survival and bone turnover (SRC family kinase inhibitors, endothelin-1 inhibitors, MET inhibitors, and thalidomide and its derivatives), inhibitors of bone turnover (bisphosphonates and receptor activator of nuclear factor-kB ligand inhibitors), antiangiogenic agents (vascular endothelial growth factor receptor and platelet-derived growth factor blockers), prostate cancer vaccines, and bone-directed radiopharmaceuticals. CONCLUSIONS With increasing data availability demonstrating tumor-bone microenvironment interactions and routine incorporation of bone-related end points into CRPC trials, bone microenvironment-targeted agents are likely to become an increasingly important component of CRPC treatment.