Controlling Tumor Microenvironment by the Antiangiogenesis Strategy

Angiogenesis occurs when the balance between negative and positive regulators inclines toward the latter, allowing the tumor and metastases to develop. Studies have found that genetic alterations may correlate with the “switching” on of angiogenic phenotypes, and that numerous soluble factors, including cytokines and matrix metalloproteinases, are key regulators of angiogenesis. The insights into this complex process gained because of the rapid, comprehensive development of the study of tumor-related angiogenesis suggest that inhibition of angiogenesis may be a useful therapeutic approach. The work of our group concentrated on this strategy in a few preclinical models. A novel matrix metalloproteinase inhibitor exhibited a potent antiangiogenesis and antimetastasis effect-stronger than that found after the use of TNP-470. In another study, interleukin-12 was found to be a strong inhibitor of angiogenesis, paralleling its key role as a mediator of the immune responses. These promising results support the antiangiogenesis approach in clinical trials for gastrointestinal tract cancer and offer a broader view of the correlation between angiogenesis and carcinogenesis in the tumor microenvironment.