After much anticipation, researchers will begin testing the effects of the tumor-starving drug endostatin in humans this week. Endostatin and a sister protein, angiostatin, first moved into public prominence when a May 3, 1998 NewYork Times cover story called them a possible revolution in cancer treatment. Endostatin and angiostatin work to shrink cancer tumors to the size of a pinhead by choking off the blood supply to cancerous tumors. Up until now, endostatin has only been tested in animals, wiping out large tumors in mice without toxic side effects. Researchers at the Dana-Farber/Partners Cancer Care in Boston are hoping for similar results in their Phase I trial with human cancer patients.
Endostatin was first discovered by Dr. Judah Folkman at Harvard and the Boston Children’s Hospital. Endostatin works by attacking a tumor’s blood vessels rather than targeting the cancer cells themselves. In animal trials, the drug has caused cancerous tumors to fall dormant or completely disappear.
Researchers have assembled a small group of cancer patients to begin the Phase I endostatin trial. In total, only about thirty patients will receive endostatin during this first trial which will focus more on possible toxic side effects of the drug. Though endostatin has been overwhelmingly successful in animal trials, researchers are skeptical that the results of these initial human trials will be extraordinary. In a recent interview, Dr. Folkman noted that many valuable cancer drugs do not demonstrate much effect in early trials. It often takes a multitude of trials to fine-tune dosages and the number of times per day or per week a drug is administered to work effectively in humans.
Cancer specialists at the M.D. Anderson Cancer Center in Houston have also announced that they will begin a similar Phase I endostatin trial in human patients in early November. A third trial will be conducted by the University of Wisconsin at Madison. Dr. James Abbruzzese of the M.D. Anderson Center has also warned the public that he does not expect to understand what endostatin will mean for cancer patients for months or even years to come.
Unlike in Boston, cancer patients who wish to be considered for the trial in Houston must phone a hotline or sign up via the Center’s website (see link below). A computer program will then randomize the list of applicants and choose a limited number of patients who will be examined to see if they are eligible for endostatin treatment. The M.D. Center hopes to recruit patients with breast, head, and neck tumors that can be easily examined by biopsy to determine the potential effectiveness of endostatin.
Like endostatin, the drug angiostatin has also been shown to shrink tumors in animal trials. Researchers at Duke University published their findings on angiostatin in the March 16, 1999 issue of Proceedings of the National Academy of Science. The study revealed that angiostatin attaches itself to the cells of blood vessels that feed the cancerous tumor. As a result, the tumor is starved and eventually disappears. Malignant tumors can kill normal tissue cells by robbing them of nutrients they need. However, the cells that compose blood vessels that nourish tumors somehow survive. Angiostatin was discovered to kill the blood vessel cells that fed cancerous tumors.
The Duke researchers found that angiostatin apparently works by attaching itself to a protein on the surface of blood vessel cells that scientists did not know existed. The protein is called ATP synthase and is normally seen only inside cells where it makes sure the cells have enough energy to operate. The researchers propose that the ATP synthase protein on the outside of blood vessel cells is what enables them to survive in a tumor, while other cells around them are dying. In theory, angiostatin blocks the protein, preventing the cells from making energy and killing them. Thus a simpler molecule that also binds to the protein could do the same job.
- For additional information on endostatin and angiostatin as well as the results of the Duke University study on angiostatin, please visit http://www.imaginis.net/cancer/news/duke_study.asp.
- The October 19, 1999 NYT Syndicate report, "Human Tests of Endostatin Set to Begin," is available online at http://www.yourhealthdaily.com/
- The May 18, 1999 ABCnews.com report, "Human Endostatin Tests Soon: Tumor-Starving Cancer Treatment," is available at http://abcnews.go.com/sections/living/DailyNews/cancer_endostatin990518.asp.
- Further information about the M.D. Anderson Cancer Center can be found at: http://www.mdanderson.org/
