Secondary bone tumors in prostate cancer: New treatments on the horizon

Sturge, Justin

Abstract

Secondary bone tumors associated with the advancement of solid tumors of the prostate and other tissue sites result in the increased risk of intractable bone pain, pathological skeletal fracture and spinal-cord compression. In addition to increasing morbidity the occurrence of metastatic bone lesions results in a marked reduction in patient survival. Once lesions have established in the bone the disease is able to progress by homotypic and heterotypic cellular interactions between the invading tumor cells and bone-associated osteoblasts and osteoclasts. The vicious cycle of bone matrix remodeling that ensues in lesions with an osteolytic phenotype is largely driven by increased osteoclast-mediated bone degradation - which leads to the subsequent loss of normal bone structure and compromised bone strength. In prostate cancer there is the additional complication of a predominantly osteosclerotic lesion phenotype - where osteoblasts become activated to overproduce a highly disorganized new bone matrix. Advances have been made in the treatment of osteolytic bone lesions - for which the currently approved treatment is the delivery of intravenous bisphosphonates or subcutaneous inhibitors of receptor activator of nuclear factor κB ligand (RANKL). Current clinical trials are focused on blocking the activity of kinases (SRC and cABL) and enzymes (cathepsin K) involved in osteolytic lesion progression. In contrast, few options exist for the treatment of osteosclerotic lesions - isolated lesions can be treated using palliative radiotherapy whereas multifocal lesions require systemic taxane-based chemotherapy. Pre-clinical and clinical studies have now started to address this shortfall in anti-osteosclerotic therapeutics and provide a significant focus of this chapter. © 2013 by Nova Science Publishers, Inc. All rights reserved.

Citation

Sturge, J. (2013). Secondary bone tumors in prostate cancer: New treatments on the horizon. In M. Berhouma (Ed.), Bone tumors: Symptoms, diagnosis and treatment (145-175). Nova Science Publishers

• Publication Date: May 1, 2013
• Deposit Date: Jun 27, 2019
• Publisher: Nova Science Publishers
• Pages: 145-175
• Series Title: Cancer etiology, diagnosis and treatments
• Book Title: Bone tumors: Symptoms, diagnosis and treatment
• ISBN: 9781626181908
• Public URL: https://hull-repository.worktribe.com/output/2015803
• Publisher URL: http://www.novapublishers.org/catalog/product_info.php?products_id=39972