Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.

Bone Metastatic Disease: Taking Aim at New Therapeutic Targets / Coluzzi, Flaminia; DI BUSSOLO, Eleonora; Mandatori, Ilenia; Mattia, Consalvo. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - 18:20(2011), pp. 3093-3115. [10.2174/092986711796391660]

Bone Metastatic Disease: Taking Aim at New Therapeutic Targets

COLUZZI, FLAMINIA;DI BUSSOLO, ELEONORA;MANDATORI, ILENIA;MATTIA, Consalvo
2011

Abstract

Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.
bone; bone resorption; cancer; cathepsin k; cxcr4; denosumab; etar; metastasis; molecular targeted therapy; osteoclasts; pain; rankl; skeletal related events; src
01 Pubblicazione su rivista::01a Articolo in rivista
Bone Metastatic Disease: Taking Aim at New Therapeutic Targets / Coluzzi, Flaminia; DI BUSSOLO, Eleonora; Mandatori, Ilenia; Mattia, Consalvo. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - 18:20(2011), pp. 3093-3115. [10.2174/092986711796391660]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/377345
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 17
social impact