Yale cancer center to test cervical cancer prevention drug: NCI grant funds research

October 14, 1999

(NEW HAVEN) -- The Yale Cancer Center has been selected by the National Cancer Institute (NCI) to conduct a clinical trial of a new drug designed to suppress infections by the human papilloma virus (HPV) so as to prevent the development of cervical cancer.

David Austin, Ph.D., assistant professor of chemistry at Yale University, first predicted on the basis of studies with colleague Rolf Loewe, Ph.D. that certain members of the indole family of compounds would suppress HPV infections. After learning that indole 3 carbinole was already under investigation by the NCI for the prevention of other cancers, he proposed that the compound be tested in preventing cervical cancer. The drug will be evaluated in a multi-institutional phase III trial of 200 people with chronic, persistent genital HPV infections, which place them at risk of cervical or anal cancer. A $1.3 million grant from the NCI will fund the clinical research study.

Genital HPV is widespread among the general population. While in most cases, the infection is cleared automatically by the body's immune system, in a small percentage of cases, it becomes persistent and requires surgical removal of the abnormal cells. Indole 3 carbinol was designed specifically to clear chronic HPV infection, and prevent cervical cancer without the need for surgery.

Albert Deissroth, associate director of clinical research at the Yale Cancer Center, worked with Austin in developing the new compound. "This is an entirely new way of making drugs, based on the molecular structure of cancer-causing genes/proteins," he said. "With the information we are now able to obtain on the cellular level, we can design drugs that are targeted specifically toward the basic defect or change in cancer cells that makes them spin out of control."

Cancer-related viruses such as Epstein Barr or HPV produce oncoproteins, which kick off the process of reproduction. By inhibiting the proteins, the tumor cells stop replicating. HPV depends on the E2 protein to keep itself going, so indole 3 carbinol was developed specifically to disable that protein so crucial to the survival of the disease. "The beauty of this approach," said Deisseroth, "is that the drug will not affect other cells in the body. It's totally nontoxic and more effective than traditional cancer treatments."

The clinical trial will test the drug in 200 people with chronic HPV infections who are at risk for cancer of the cervix or anus, but are not at the point where surgery is indicated. Because HPV warts are a major problem in people with suppressed immune systems, half the study participants will be individuals who are HIV positive. The drug, or a placebo, will be taken daily for eight weeks, during which time participants will be examined weekly for signs of toxicity.

Specimens taken from patients will be analyzed in the laboratory of Janet Brandsma, Ph.D., associate professor of comparative medicine at the Yale University School of Medicine. "We will try to determine whether the type or quantity of HPV present influences the response of lesions to the treatment," she said.

More than 10 million American women are infected with high-risk HPVs, and an estimated 15,000 American women are diagnosed with cervical cancer each year. While routine Pap screening has significantly reduced the rate of cervical cancer in this country, it remains a leading cause of cancer death in many other parts of the world. There are approximately 500,000 cases of cervical cancer worldwide each year -- about one-third of them fatal.

Deisseroth credits the Cancer Center with providing the environment that brought together researchers from several different disciplines to collaborate on what he believes will be a successful project. "If not for the Cancer Center, I would not have hooked up with David Austin in the first place. Animal testing was possible because of a rabbit model developed by Janet Brandsma. The Cancer Center provided funding to keep the project going, and the result -- at the very least -- is a clinical trial."
The Yale Cancer Center is one of a select network of comprehensive cancer centers in the country designated by the National Cancer Institute and the only one in Southern New England. Bringing together the resources of Yale-New Haven Hospital and the Yale University School of Medicine, its mission encompasses patient care, research, cancer prevention and control, community outreach and education. The Cancer Information Service, a Yale Cancer Center program funded by the National Cancer Institute, provides up-to-date information on cancer prevention, detection and treatment. Trained cancer information specialists are available to answer questions Monday through Friday from 9:00 a.m. to 4:00 p.m. at 1-800-4-CANCER (1-800-422-6237).

Yale University

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