1. Academic Validation
  2. Bone-Targeted Therapies in Cancer-Induced Bone Disease

Bone-Targeted Therapies in Cancer-Induced Bone Disease

  • Calcif Tissue Int. 2018 Feb;102(2):227-250. doi: 10.1007/s00223-017-0353-5.
Sofia Sousa 1 2 Philippe Clézardin 3 4 5
Affiliations

Affiliations

  • 1 National Institute of Health and Medical Research (INSERM), UMR 1033, 69372, Lyon, France. sofia.sousa@inserm.fr.
  • 2 Faculty of Medicine Laennec, University of Lyon-1, 69372, Villeurbanne, France. sofia.sousa@inserm.fr.
  • 3 National Institute of Health and Medical Research (INSERM), UMR 1033, 69372, Lyon, France.
  • 4 Faculty of Medicine Laennec, University of Lyon-1, 69372, Villeurbanne, France.
  • 5 European Cancer and Bone Metastasis Laboratory, Department of Bone Oncology and Metabolism, Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK.
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

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

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