Factors promoting tumor angiogenesis

Among the multitude of positive factors that have been described, VEGF stands out as the most commonly associated factor with the various aspects of tumor angiogenesis. It interacts or is associated with many other positive regulators, as seen in Table 1. Accordingly, several of the current antiangiogenic approaches to tumor control involve its inhibition. The evaluation of antiangiogenic therapies may help to sort out the relative contributions of these positive factors. Many questions are still unanswered. Will the inhibition of VEGF control most malignancies? Will multiple factors need to be inhibited to achieve effective tumor management? How significant will the problem of redundancy become during persistent hypoxic stimulation of tumor angiogenesis as one factor, such as VEGF, remains inhibited? Will the inhibition of different positive factors be needed at different stages of tumor development, such as in large well-developed tumors that may have better established and larger vessels v. early small tumors with only poorly developed microvessels? Will enhancement of naturally occurring angiogenic inhibitors, such as angiostatin and endostatin, be as effective (or more effective) than inhibition of the positive factors? Will synergistic effects be seen by enhancing natural inhibition and also inhibiting positive factors of tumor angiogenesis? Also, what will the effects of antiangiogenic agents be once they are systemically distributed, such as when treating or preventing metastatic disease? As stimulating conditions and factors for angiogenesis in tumors become better understood, then the therapies available for managing them will improve.