Angiogenesis and its inhibitors.

The hypothesis that solid tumors are angiogenesis-dependent has, in the past decade, generated much new work aimed at understanding the mechanism of angiogenesis itself. Many laboratories in this country and abroad are now studying some aspect of this intriguing problem. Some investigations are focused mainly on tumor angiogenesis, whereas others are centered on angiogenesis that occurs in physiologic situations or that dominates certain non-neoplastic pathologic states. These efforts have brought about [a] the development of bioassays for angiogenesis; [b] the partial purification (and in one case the complete purification) of angiogenic factors from neoplastic and non-neoplastic cells; [c] the development of new polymer technology for the sustained release of these factors and of other macromolecules in vivo; [d] the cloning and long-term culture of capillary endothelial cells; [e] the demonstration of the role of nonendothelial cells, such as mast cells, in modulating angiogenesis; [f] the discovery of angiogenesis inhibitors; and [g] the recent demonstration that certain animal tumors will undergo complete regression when treated by antiangiogenesis alone. The effects of angiogenesis inhibitors provide the most compelling evidence for the role of angiogenesis in tumor growth. That it is now possible not only to inhibit tumor growth but also to eradicate some experimental tumors speaks strongly for a therapeutic approach that may some day be useful in clinical oncology. Conceivably, the original goal to understand the role of angiogenesis in tumor growth will lead to the use of angiogenesis inhibitors in other non-neoplastic diseases.