REVIEW  BONE METASTASES IN THE ERA OF TARGETED TREATMENTS 

The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2019 June;63(2):98-111

DOI: 10.23736/S1824-4785.19.03203-5

Copyright © 2019 EDIZIONI MINERVA MEDICA

language: English

Bone metastases in the era of targeted treatments: insights from molecular biology

Jonatan DEWULF ¹, Christel VANGESTEL ^{1, 2}, Yannick VERHOEVEN ³, Peter van DAM ^{3, 4}, Filipe ELVAS ¹, Tim Van den WYNGAERT ^{1, 2} ✉, Philippe CLÉZARDIN ^{5, 6}

¹ Molecular Imaging Center Antwerp (MICA), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium; ² Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium; ³ Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Belgium; ⁴ Multidisciplinary Oncologic Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium; ⁵ INSERM Laboratory Pathophysiology, Diagnosis and Treatments of Bone Diseases, Lyon, France; ⁶ INSERM European Associated Laboratory Cancer and Bone Metastasis, University of Sheffield, Medical School, Sheffield, UK

Bone metastases remain a common feature of advanced cancers and are associated with significant morbidity and mortality. Recent research has identified promising novel treatment targets to improve current treatment strategies for bone metastatic disease. This review summarizes the well-known and recently discovered molecular biology pathways in bone that govern normal physiological remodeling or drive the pathophysiological changes observed when bone metastases are present. In the rapidly changing world of targeted cancer treatments, it is important to recognize the specific treatment effects induced in bone by these agents and the potential impact on common imaging strategies. The osteoclastic targets (bisphosphonates, LGR4, RANKL, mTOR, MET-VEGFR, cathepsin K, Src, Dock 5) and the osteoblastic targets (Wnt and endothelin) are discussed, and the emerging field of osteo-immunity is introduced as potential future therapeutic target. Finally, a summary is provided of available trial data for agents that target these pathways and that have been assessed in patients. The ultimate goal of research into novel pathways and targets involved in the tumor-bone microenvironment is to tackle one of the great remaining unmet needs in oncology, that is finding a cure for bone metastatic disease.

KEY WORDS: Bone remodeling; Bone and bones; Therapeutics; Physiopathology