Novel therapeutic strategy for osteosarcoma targeting osteoclast differentiation, bone- resorbing activity and apoptosis pathway

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Akiyama, Toru, Dass, Crispin R and Choong, Peter F. M (2008) Novel therapeutic strategy for osteosarcoma targeting osteoclast differentiation, bone- resorbing activity and apoptosis pathway. Molecular Cancer Therapeutics, 7 (11). pp. 3461-3469. ISSN 15357163

Abstract

Osteosarcoma is the most common bone sarcoma, which mainly affects adolescents and young adults. Although the combination of modern surgery and systemic chemotherapy has improved osteosarcoma treatment dramatically, no substantial change in survival has been seen over the past 20 years. Therefore, novel therapeutic strategies for osteosarcoma are required if the 35% of patients with fatal metastases are to be successfully treated. Recently, osteoclasts have drawn attention as a therapeutic target in various bone disorders including osteosarcoma. The osteoclast is the sole cell that resorbs bone and is central in pathologic situations, where bone destruction is intricately involved. Osteosarcoma cells are of the osteoblastic lineage, the latter of which is characterized by cells secreting the osteoclast-inducing factor, receptor activator of nuclear factor-KB ligand. Hence, osteosarcoma is a better candidate for osteoclast-targeted therapy than other primary and metastatic bone tumors. The rapid progress on the molecular mechanism regulating osteoclast has propelled a development of new therapeutic approaches. In this review article, we present the prospects of osteoclast-targeted therapy as a novel treatment strategy for osteosarcoma. Receptor activator of nuclear factor-KB-Fc, osteoprotegerin, bisphosphonates, and Src inhibitor are shown as positive candidates and can control various aspects of osteoclast function.

Item type Article
URI https://vuir.vu.edu.au/id/eprint/3466
Official URL http://dx.doi.org/10.1158/1535-7163.MCT-08-0530
Subjects Historical > FOR Classification > 1199 Other Medical and Health Sciences
Historical > Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Keywords ResPubID18869. osteosarcoma, bone sarcoma, multidisciplinary therapy, malignant tumor of bone
Citations in Scopus 128 - View on Scopus
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