Angiogenesis and hepatic colorectal metastases.

Angiogenesis is a critical step in the metastatic cascade of colorectal cancer. Several angiogenesis inhibitors have been evaluated in animal models and have shown efficacy, but challenges remain in using these drugs effectively in the clinical setting. Although several of these angiogenesis inhibitors are currently being evaluated in clinical trials, alone or in combination with cytotoxic chemotherapy, early results suggest that angiogenesis inhibitors alone, when used for advanced disease, have minimal activity. It is likely that this class of drugs will prove more efficacious when used either in the setting of minimal disease as agents that may promote tumor dormancy or in combination with other conventional forms of therapy. In addition, strategies such as metronomic therapy have been proposed whereby lower doses of cytotoxic chemotherapy, given more frequently, may act via an antiangiogenic mechanism [67,68]. Another challenge is identifying methods of assessing response to antiangiogenic therapy. To date, traditional methods of identifying response to treatment have not proven effective. Several investigators are working toward identifying circulating endothelial or tumor-associated factors that may be useful in following treatment. Novel imaging techniques are also being evaluated with enhanced CT and MRI, and newer modalities. Hepatic colorectal metastases provide an opportune setting in which to accomplish these challenges because the high incidence of disease and the ability to measure tumor with a variety of techniques lend themselves to evaluation of antiangiogenic therapy.