title: Emerging drugs for the treatment of bone metastasis.
abstract: BACKGROUND
  Bone metastases are virtually incurable resulting in significant disease morbidity, reduced quality of life and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Increased understanding of the pathogenesis of bone disease has led to the discovery and clinical utility of bone-targeted agents other than bisphosphonates and denosumab, currently, the standard of care in this setting.
  
  
  METHODS
  In this review, we present the recent advances in molecular targeted therapies focusing on therapies that inhibit bone resorption and/or stimulate bone formation and novel anti-tumoral agents that exerts significant effects on skeletal metastases, nowadays available in clinical practice or in phase of development.
  
  
  CONCLUSIONS
  New emergent bone target therapies radium-223, mTOR inhibitors, anti-androgens have demonstrated the ability to increase overall survival in bone metastatic patients, other compounds, such as ET-1 and SRC inhibitors, up to now failed to clearly confirm in clinical trials their promising preclinical data.
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pantano
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Iuliani
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Alice
authors.initials: A
authors.lastname: Zoccoli
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Fioramonti
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Delia
authors.initials: D
authors.lastname: De Lisi
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Fioroni
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ribelli
authors.affiliation: b 2 Università Politecnica delle Marche, AOU Ospedali Riuniti, Medical Oncology Department , Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.affiliation: a 1 Campus Bio-Medico University of Rome, Medical Oncology Department , Via Alvaro del Portillo 200, 00128 Rome, Italy +39 062 254 191 17 ; +39 062 254 119 33; m.iuliani@unicampus.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D000069448:Denosumab / Q000494:pharmacology / Q000627:therapeutic use; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D015996:Survival Rate; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000069448:Denosumab
keywords: bone metastases; bone target therapy; osteoblast; osteoclast