title: Bone targeted therapies in metastatic castration-resistant prostate cancer.
abstract: Prostate cancer is the most common male cancer. About 90% of metastatic patients will develop bone metastases. Bone disease is responsible of pain, deterioration of quality of life and serious bone complications. Proliferation of prostate cancer cells in the bone marrow induces osteoclast activation and osteolysis. Targeting the bone microenvironment reduces morbidity. Relevant preclinical and clinical studies of bone-targeted therapies in castration-resistant prostate cancer were identified in PubMed and clinical trial databases. Different drugs are available or in development that target bone resorption (bisphosphonates, RANK ligand inhibitors), bone formation (endothelin 1 inhibitors), cancer cell migration (SRC-family kinase inhibitors, vascular endothelial growth factor-MET inhibitors), and survival (radiopharmaceuticals). In phase III trials, zoledronic acid, denosumab, and radium-223 were shown to significantly delay skeletal-related events. Radium-223 was also shown to improve overall survival. Biomarkers of bone resorption (urinary N-telopeptide) and bone making (alkaline phosphatase) have an independent prognostic impact. Targeting the bone microenvironment is an important component of castration-resistant prostate cancer management to reduce bone complications and improve overall survival. Biomarkers of bone turnover have an independent prognostic impact.
authors: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Sud, 94800 Villejuif Cedex, France. shanna.rajpar@igr.fr
authors: Shanna
authors: S
authors: Rajpar
authors: Karim
authors: K
authors: Fizazi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001842:Bone and Bones / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000494:pharmacology / Q000627:therapeutic use; D017154:Stromal Cells / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D047428:Protein Kinase Inhibitors; D019275:Radiopharmaceuticals; D019061:src-Family Kinases