The effects of angiostatin and endostatin on mechanisms regulating angiongenesis in other processes besides tumor growth is one area of research that requires additional study, according to noted University of Notre Dame blood chemist Francis J. Castellino.
Basic research conducted in Castellino's laboratory contributed to the identification of angiostatin, one of the promising new cancer drugs being heralded nationally this week. Angiostatin and endostatin are being given top priority by the National Cancer Institute and will be rushed to clinical trial in humans.
Castellino is very excited about the drugs' possibilities but cautions that more studies involving the basic science of these drugs are needed. Research now under way in Castellino's laboratories will attempt to address some of these issues.
Castellino, whose laboratory is without question one of the top handful studying blood clotting mechanisms, is Kleiderer-Pezold professor of biochemistry, dean of Notre Dame's College of Science, and director of the Center for Transgene Research and the Walther Cancer Center, which are also at the University. It was his antibody to plasminogen, a precurser of the clot-dissolving enzyme plasmin -- as well as a number of basic studies on plasminogen fragments -- that helped confirm angiostatin is a fragment of this protein. (Endostatin is derived from a different, unrelated protein, collagen XVIII.)
Angiostatin and endostatin were discovered in the laboratory of Dr. Judah Folkman, a cancer researcher at Children's Hospital in Boston. The drugs function by cutting off the blood supply to tumors, making even extremely large tumors disappear. In mice, the drugs appear to stop malignant tumor growth and spreading, but they have not yet been tested in humans, and the medical community remains cautious.