ABSTRACT
The recognition that prostate cancer cells preferentially metastasize to the skeleton in patients with advanced disease has led to the development of new therapies not only directed to the cancer cell, but also specifically targeted towards altering the bone microenvironment into a less favorable ‘‘soil’’ for tumor growth and survival. These new and exciting strategies are based around three key concepts that describe the processes involved in tumor metastasis to bone: the first is that prostate cancer cells preferentially bind to endothelial cells in the marrow sinusoids in a way that allows them to be retained and to enter the bone marrow proper. The second is that once tumor cells have passed through the sinusoid walls into the marrow they benefit from growth and/or survival factors already present in this environment, with the marrow acting as a ‘fertile soil.’ The third concept is that when established in bone, prostate cancer cells become involved in a so-called ‘‘vicious cycle’’ where they induce modification of bone turnover resulting in the increased production or release of factors that benefit their growth. Suppression of the latter process has been the focus of some of the most recent advances in bone-directed therapies for prostate cancer. This chapter will review these new approaches and their efficacy, but will also discuss developments in other areas that might be exploited to suppress prostate cancer growth in bone.
