Published Autumn 1998
An assist in discovery of anti-cancer drug
If a new drug derived from mouse urine can starve malignant tumors to death in humans the way it appears to in mice, humanity will owe a part of its thanks to Notre Dame scientists.
Basic research conducted in the laboratory of blood chemist Francis J. Castellino contributed to the identification of angiostatin, a promising new cancer drug heralded on the front page of The New York Times and in other national publications earlier this year. Because of its success in tests on mice, angiostatin -- along with another drug, endostatin -- is being rushed into clinical trials in humans.
Angiostatin and endostatin were discovered in the laboratory of Judah Folkman, a cancer researcher at Children's Hospital in Boston. The drugs have been shown to cut off the supply of blood to tumors, making even large tumors disappear. The drugs apparently interfere with a tumor's ability to synthesize new capillaries from existing blood vessels, a process called angiogenesis
Capillary-building is common in the womb, but it normally takes place later in life only during activities like wound repair or with skin grafts. Among the many questions needing to be answered is how angiostatin and endostatin might affect a necessary bodily function like wound repair, says Castellino, Kleiderer-Pezold professor of biochemistry and dean of ND's College of Science.
One of the nation's leading researchers in the field of blood-clotting mechanisms, Castellino is also director of the Walther Cancer Center and the Center for Transgene Research, which are located at the University. The Transgene center supplied an antibody to Folkman's lab that allowed the lab to trace angiostatin's chemical origins to the protein plasminogen, a precursor of the clot-dissolving enzyme plasmin.
The Transgene and Walther centers are currently collaborating with the Cleveland Clinic on mouse trials to learn more about the angiostatin-plasminogen relationship in cancer.