title: Emerging therapies in metastatic bone pain.
abstract: BACKGROUND
  Current treatment for metastatic bone pain is mainly palliative. Recent insights into the molecular mechanisms involved in bone metastases have led to the identification of promising therapeutic targets. This review offers an update of preclinical and clinical data on new drugs for metastatic bone pain.
  
  
  METHODS
  Biphosphonates are the gold standard of bone-targeted therapy in bone metastases, for their anti-resorptive and analgesic effects. New drugs aim at breaking the 'vicious cycle' of bone metastatic disease, due to the bidirectional interaction between cancer cells and bone microenvironment. Osteoprotegerin, RANK/RANKL interaction, cathepsin K, the Wnt/beta-catenin pathway and sclerostin are emerging targets for modulation of cancer-induced bone desorption. Other promising targets are those expressed in cancer cells that metastasize to bone, including Src, nerve growth factor, endothelin A, TGF-beta and CXCR4. Interesting therapeutic options include targets on nociceptors that innervate the bone, such as TPRV1, Trk and cannabinoid receptors.
  
  
  CONCLUSIONS
  Emerging therapies promise, in the next 10 years, a significant expansion in the array of therapeutic options for bone metastases. Most of these drugs are still in an early phase of development. Further clinical trials are needed to support the evidence of their efficacy and tolerability profile.
authors.affiliation: SAPIENZA University of Rome, Department of Medical and Surgical Sciences and Biotechnologies, Italy. flaminia.coluzzi@uniroma1.it
authors.forename: Flaminia
authors.initials: F
authors.lastname: Coluzzi
authors.forename: Ilenia
authors.initials: I
authors.lastname: Mandatori
authors.forename: Consalvo
authors.initials: C
authors.lastname: Mattia
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000556:secondary; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic