title: Targeted Agents in Preclinical and Early Clinical Development for the Treatment of Cancer Bone Metastases.
abstract: BACKGROUND
  Bone is one of the preferential organs affected in patients with metastatic cancers. Bone metastases contribute substantially to morbidity and mortality in cancer patients, especially for those with breast and prostate cancer. Bisphosphonates and denosumab, potent inhibitors of osteoclastic bone resorption, are the current standard of care for bone metastases; however, their effects are palliative. Recent preclinical studies have revealed a variety of potential targets for the development of novel therapeutic agents. Some of these are currently being evaluated in clinical trials.
  
  
  METHODS
  This paper reviews the preclinical and early clinical development of molecularly targeted agents for the treatment of bone metastases. The agents are categorized according to their targets, osteoclasts, osteoblasts, metastatic cancer cells, and the bone microenvironment.
  
  
  CONCLUSIONS
  Recent advances in our understanding of the molecular and cellular mechanisms of bone metastases have led to the development of novel therapeutic options. Although most of their effects have yet to be proved in clinical studies, it is the author's belief that they will contribute significantly to improving the treatment outcome of patients with bone metastases in the near future.
authors.affiliation: a Department of Histology and Cell Biology , Matsumoto Dental University , Shiojiri , Nagano , Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hiraga
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D050071:Bone Density Conservation Agents
keywords: bone metastasis; bone microenvironment; cancer; clinical development; osteoblasts; osteoclasts