Anti-angiogenesis therapy: concepts and importance of dosing schedules in clinical trials

The biological control of angiogenesis is critical to the clinical control of cancer. Understanding the mechanism of formation and regulation of new b lood vessel development would open a new avenue for cancer treatment. Inten se research effort has revealed a variety of factors which initiate, contro l and terminate the multi-stage process of angiogenesis, as well as target structures which interfere with this process. Protease inhibitors, inhibito rs of the endothelial cell proliferation, suppressors of angiogenic growth factors, copper chelators, and other compounds interfering with the process of angiogenesis were screened for inhibition of tumor angiogenesis and som e of them are in clinical trials. Very recently, a new term,'metronomic dos ing regimen' has been introduced, which implicates the use of the old cytos tatic anticancer agents as anti-angiogenic agents. Results from recent stud ies will be discussed briefly and the prospects of inhibition of tumor angi ogenesis as a new treatment modality will be outlined.