Mechanisms Underlying Osteolytic and Osteoblastic Bone Metastases

Bone is a common site of metastasis for some of the most aggressive cancers. Bone metastasis is rarely curative and is associated with poor prognosis and a high rate of mortality. When cancer metastasizes to bone, it deregulates bone resorption and/or bone formation usually resulting in a net bone loss or osteolysis. However, bone metastases are highly heterogeneous, and patients will present with both osteolytic and osteoblastic lesions, histologically. The molecular basis of this preferential growth of cancer cells in the bone microenvironment has been an area of active investigation. Here, we will highlight some of the progress that has been made in identifying key molecular mechanisms underlying this process, as well as recognize area of investigation that continue to escape our current understanding and remain to be elucidated. We describe some of the unique characteristics of the bone niche that have been shown to aid the cancer cells in the homing process and create a microenvironment conducive for cancer cells to colonize. We also describe newly identified cancer-derived regulatory factors that modulate bone metabolism, contributing to mineral destruction and aberrant bone formation. This complex bidirectional interplay between tumor cells and bone microenvironment establishes a “vicious cycle” that leads to a selective growth advantage for the cancer cells. Here, we will also describe current innovative therapeutic approaches that utilize recent knowledge of the cancer-metastatic bone microenvironment and are likely to contribute to future drug designs.