29 MAY 1998. Is a cancer cure on the horizon? That was the question raised on May 3 by a front-page article in The New York Times (see "A Cautious Awe Greets Drugs..." in the bibliography).
The article described a pair of new chemicals -- known by the lip-wracking name "angiogenesis inhibitors" -- now being tested against cancer in laboratory mice. Unlike existing drugs, which target tumor cells directly, these naturally occurring proteins prevent the growth of blood vessels that small tumors need to grow and become dangerous.
The article sparked a hoopla that's correct in at least one respect: A cancer cure may finally be at hand -- for mice. Although nobody knows if the angiogenesis inhibitors will help people, Richard Klausner, director of the National Cancer Institute, calls them the "single most exciting thing on the horizon" for treating cancer. "I am putting nothing on higher priority than getting this into clinical trials."
Courtesy of Jackson Laboratory, Bar Harbor, Maine.
| U P D A T E 23 MARCH 1999. The University of Wisconsin Comprehensive Cancer Center is one of two sites to conduct human tests of endostatin, a promising potential cancer treatment that seems to work in part by disrupting the growth of blood vessels that nourish tumor cells. The trials will be "Phase 1" tests in which researchers will try to discover the maximum dose patients can tolerate without undue toxicity. Initially, three to six patients will receive small doses of the drug and will be carefully monitored for toxic effects. Additional patients will then receive graduated doses of the drug. All patients will be carefully monitored through a variety of complex tests. |
The fascination with angiogenesis reflects a growing recognition that solid tumors (and even some blood cancers) can't grow beyond barely visible size until they get new blood vessels through the process of angiogenesis. In fact, many tumors remain at that relatively innocuous stage for years, and only become dangerous if and when they acquire blood circulation.
Many angiogenesis inhibitors have been identified over the past few years. The 11 inhibitors that are now being tested in human volunteers are all artificial, unlike the naturally occurring angiostatin and endostatin. (Anti-angiogenesis drugs could also be useful in many eye diseases, where unwanted growth of blood vessels in the retina is common, and such other illnesses as arthritis.)
Despite the ongoing tests with artificial angiogenesis inhibitors, it was the discovery of endostatin, the most potent inhibitor yet, that spurred the recent hoopla.
Hoopla? What does endostatin do?
A major advantage
The angiogenesis work depends on the fact that tumors control blood vessel growth by secreting small amounts of stimulatory or inhibitory chemical messengers. When enough inhibitor is present, the tumor seems to remain small and harmless. The danger begins when the balance shifts toward "growth," and blood vessels bring new nutrients to the tumor. That's when the primary tumor grows, and some cells depart to form metastases (satellite tumors) elsewhere in the body.
