Bone-Targeted Therapies in Cancer-Induced Bone Disease

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 main...

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Veröffentlicht in:Calcified tissue international 2018-02, Vol.102 (2), p.227-250
Hauptverfasser: Sousa, Sofia, Clézardin, Philippe
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description 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.
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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. 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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. 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subjects Androgen Antagonists - therapeutic use
Biochemistry
Biomedical and Life Sciences
Bisphosphonates
Bone cancer
Bone diseases
Bone growth
Bone Neoplasms - drug therapy
Bone Neoplasms - secondary
Bone resorption
Bortezomib - therapeutic use
Cancer
Cancer therapies
Cathepsin K - antagonists & inhibitors
Cell Biology
Denosumab - therapeutic use
Diphosphonates - therapeutic use
Endocrinology
Humans
Immunotherapy
Integrins - antagonists & inhibitors
Life Sciences
Metastases
Metastasis
Molecular Targeted Therapy
Monoclonal antibodies
Morbidity
Orthopedics
Osteoblasts
Osteoclasts
Osteogenesis
Proteasome inhibitors
Proteasome Inhibitors - therapeutic use
Proto-Oncogene Proteins pp60(c-src) - antagonists & inhibitors
Quality of life
Radiopharmaceuticals - therapeutic use
Review
Targeted cancer therapy
TOR Serine-Threonine Kinases - antagonists & inhibitors
Tumors
title Bone-Targeted Therapies in Cancer-Induced Bone Disease
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