Abstract
Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenomenon triggered by tumor cells eventually leading to both tumor proliferation as well as bone deregulation, thus fueling the development of bone metastasis. The complex network, linking tumor cells to the bone by activating osteoclasts, represents a fruitful target for the treatment of bone metastases. In this review we will describe how tumor cells perturb the bone microenvironment by actively influencing osteoclast formation and activity. Moreover, we will describe the current antiresorptive drugs employed in the treatment of bone metastases as well as new, targeted therapies able to affect both cancer cells and osteoclasts.
Highlights
Bone MetastasesMetastasis is, so far, an incurable disease. The skeleton is one of the most frequent sites of metastases, behind the lungs and liver [1]
Bone metastases are frequently the final fate of breast and prostate cancer patients
Other inputs can come from micro-fractures or the release of cytokines, like insulin-like growth factor (IGF), tumor necrosis factor (TNF) α, parathyroid hormone (PTH) and interleukin (IL) 6, which in turn promote the detachment of the lining cells from the bone surface and the exposition of the latter for the subsequent step of erosion [12]
Summary
Metastasis is, so far, an incurable disease. The skeleton is one of the most frequent sites of metastases, behind the lungs and liver [1]. In breast and prostate cancers, those patients with unique metastases in the bone represent as a distinct subset of metastatic patients with a better prognosis than those with liver or lung metastases. Mechanical pain is caused by the pressure exerted by tumor mass within the bone, associated with loss of bone strength They are not effective in increasing survival, current antiresorptive agents and radiotherapy reduce bone pain, significantly improving patient’s quality of life [8]. Osteolytic lesions are preferentially caused by breast cancer cells and are characterized by the complete destruction of bone and its substitution with a tumor mass. Osteosclerotic metastases are usually preceded, and likely triggered, by an exacerbated osteoclast activation This explains why the current antiresorptive therapies are effective in this type of bone metastasis. Whichever histopathological kind of bone metastases, all are determined by a deregulation of bone homeostasis caused by tumor cells
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