Targeting Factors Involved in Bone Remodeling as Treatment Strategies in Prostate Cancer Bone Metastasis

Abstract

Prostate cancer is the most commonly diagnosed cancer in men within the western world and the third leading cause of cancer-related deaths. Even if the cancer is considered localized to the prostate, there is a 15% to 20% incidence of subsequent metastatic disease. Prostate cancer has a very high proclivity for metastasizing to bone, with f90% of men with advanced disease having skeletal lesions. The prostate cancer metastases are characteristically osteoblastic, with extensive new bone deposition, unlike other tumors that metastasize to bone and cause an osteolytic response reflective of bone degradation. There are a considerable number of studies relating to inhibition of the osteoblastic response, including interference with endothelin-1, bone morphogenetic proteins, and Wnt signaling pathways.Within the past few years, several studies showed that increased osteolytic activity also occurs in the background of the prostate cancer skeletal metastases. Because growth factors are being released from the bone matrix during degradation, it suggests that inhibition of osteolysis might be effective in slowing tumor growth. Several strategies are being developed and applied to affect directly the osteolytic events, including use of bisphosphonates and targeting the critical biological regulators of osteoclastogenesis, receptor activator of nuclear factor-nB and receptor activator of nuclear factor-nB ligand. This review focuses on several of the clinical and preclinical strategies to inhibit the growth of prostate cancer cells in bone and to alleviate the multitude of associated skeletal-related events.

Prostate Cancer, Serum Parathyroid Hormone, and the Progression of Skeletal Metastases

“…The growth of blastic metastases establishes a vicious cycle of high PTH, high bone turnover, and increased morbidity and mortality from the consequences of bony remodeling. that underlie the survival benefit is important because this benefit conceivably could be achieved with lower, potentially less toxic doses of calcitriol/calcitriol analogues as well as by other means (62).…”

Src as a therapeutic target in men with prostate cancer and bone metastases

“…Depending on whether mechanisms favour a dominant osteoclastic or osteoblastic response, bone metastasis in cancer produces a primarily osteolytic or osteoblastic clinical presentation [2]; however, the underlying aetiology is complex and incompletely understood, and there might be both histological and phenotypic heterogeneity [8].…”

Arachidonic acid modulates the crosstalk between prostate carcinoma and bone stromal cells

“…At the same time, PCa cells mimic in some instances bone cells perturbing the normal process of bone remodeling and providing a niche in which they can grow and expand. Clinical evidence of bone metastasis from PCa demonstrates the existence of an intense crosstalk between cancer and bone cells resulting in mixed bone lesions controlled by an aberrant activation of osteoblasts and osteoclasts (Vessella & Corey 2006). Thus, the molecular interaction between bone and tumor cells appears to be a critical step in the growth of metastatic cells in the bone.…”