Clezardin, P. orcid.org/0000-0003-0149-4463, Coleman, R., Puppo, M. et al. (5 more authors) (2021) Bone metastasis : mechanisms, therapies and biomarkers. Physiological Reviews, 101 (3). pp. 797-855. ISSN 0031-9333
Abstract
Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability), which negatively affect the patient's quality of life. Here, we first discuss the burden of skeletal complications in cancer bone metastasis. We then describe the pathophysiology of bone metastasis. Bone metastasis is a multistage process; long before the development of clinically detectable metastases, circulating tumor cells settle and enter a dormant state in normal vascular and endosteal niches present in the bone marrow, which provide immediate attachment and shelter, and only become active years later as they proliferate and alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. The molecular mechanisms involved in mediating each of these steps are described and we also explain how tumor cells interact with a myriad of interconnected cell populations in the bone marrow, including a rich vascular network, immune cells, adipocytes and nerves. We discuss metabolic programs that tumor cells could engage with to specifically grow in bone. We also describe the progress and future directions of existing bone-targeted agents and report emerging therapies that have arisen from recent advances in our understanding of the pathophysiology of bone metastases. Finally, we discuss the value of bone turnover biomarkers in detection and monitoring of progression and therapeutic effects in patients with bone metastasis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Physiological Reviews. This is an author-produced version of a paper subsequently published in Physiological Reviews. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | bone resorption; immune surveillance; metastatic niche; osteomimicry; tumor cell dormancy |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Jan 2021 09:36 |
Last Modified: | 28 Jan 2022 14:29 |
Status: | Published |
Publisher: | American Physiological Society |
Refereed: | Yes |
Identification Number: | 10.1152/physrev.00012.2019 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:170088 |