The elucidation of the interaction of the tumor and its microenvironment has increased surgeons' understanding of the biologic mechanisms mediating metastases formation. The ability to develop effective biologic therapies will depend on understanding the complex interactions among endothelial cells and tumor cells and on the cytokine cross-talk among all cells within a particular tumor at a particular site. Biologic therapies must be targeted to both the site and the tumor. By the time metastases form, most steps in the metastatic cascade have been completed. Therapy to down-regulate or interrupt the last stages of metastases, proliferation, and angiogenesis and mechanisms to disrupt cell survival signals appear to be the most promising areas of investigation.
