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Calcified Tissue International

, Volume 102, Issue 2, pp 227–250 | Cite as

Bone-Targeted Therapies in Cancer-Induced Bone Disease

  • Sofia Sousa
  • Philippe Clézardin
Review

Abstract

Cancer-induced bone disease is a major source of morbidity and mortality in cancer patients. Thus, effective bone-targeted therapies are essential to improve disease-free, overall survival and quality of life of cancer patients with bone metastases. Depending of the cancer-type, bone metastases mainly involve the modulation of osteoclast and/or osteoblast activity by tumour cells. To inhibit metastatic bone disease effectively, it is imperative to understand its underlying mechanisms and identify the target cells for therapy. If the aim is to prevent bone metastasis, it is essential to target not only bone metastatic features in the tumour cells, but also tumour-nurturing bone microenvironment properties. The currently available bone-targeted agents mainly affect osteoclasts, inhibiting bone resorption (e.g. bisphosphonates, denosumab). Some agents targeting osteoblasts begin to emerge which target osteoblasts (e.g. romosozumab), activating bone formation. Moreover, certain drugs initially thought to target only osteoclasts are now known to have a dual action (activating osteoblasts and inhibiting osteoclasts, e.g. proteasome inhibitors). This review will focus on the evolution of bone-targeted therapies for the treatment of cancer-induced bone disease, summarizing preclinical and clinical findings obtained with anti-resorptive and bone anabolic therapies.

Keywords

Bone metastasis RANKL Sclerostin DKK1 Bisphosphonates mTOR inhibitors Denosumab Romosozumab Radium 223 Cathepsin k inhibitors c-Src inhibitors 

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.National Institute of Health and Medical Research (INSERM), UMR 1033LyonFrance
  2. 2.Faculty of Medicine LaennecUniversity of Lyon-1VilleurbanneFrance
  3. 3.European Cancer and Bone Metastasis Laboratory, Department of Bone Oncology and Metabolism, Mellanby Centre for Bone ResearchUniversity of SheffieldSheffieldUK

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