Abstract
Prostate cancer (CaP) is the most frequently diagnosed cancer in men and the second leading cause of cancer death among men in the United States (1). The most common site of CaP metastasis is the bone with skeletal metastases identified at autopsy in up to 90% of patients dying from CaP. Understanding how tumor interacts with bone may lead toward identifying therapies to prevent or diminish the consequences of bone metastases. CaP forms a mixture of osteolytic (excess bone resorption) and osteoblastic (excess bone production) bone metastases. The osteolytic component of bone metastases is caused, in part, through cancer-mediated activation of the receptor of nuclear factor-κ B ligand (RANKL) pathway. Blocking RANKL has been shown to successfully inhibit establishment or progression of CaP bone metastases in animal models. Other factors that are important in the development of CaP-induced osteolytic lesions include interleukin (IL)-6, parathyroid hormonerelated protein (PTHrP), and matrix metalloproteinases (MMPs). The mechanism through which CaP induces osteoblastic lesions is less clear; however, CaP produces a variety of factors that may promote an overall osteoblastic phenotype, including an inhibitor of RANKL, osteoprotegerin (OPG); a vascular-active agent, endothelin (ET)-1; and transforming growth factor (TGF)-β. Several methods to target CaP bone metastases are being explored in clinics, including bisphosphonates, inhibitors of RANKL and ET-1. To effectively treat CaP bone metastases, targeting both the osteolytic and osteoblastic components simultaneously may be important.
Key Words
References
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Keller, E.T. (2007). Biology and Therapeutic Basis of Prostate Cancer Bone Metastasis. In: Chung, L.W.K., Isaacs, W.B., Simons, J.W. (eds) Prostate Cancer. Contemporary Cancer Research. Humana Press. https://doi.org/10.1007/978-1-59745-224-3_11
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