Researchers Unearth New Clues to Tumor Growth

August 1, 1997 1:19 PM EDT

By David Morgan

PHILADELPHIA (Reuter) - A team of U.S. and Italian researchers has uncovered new clues about how cancer-causing agents, such as viruses, cigarette smoke and environmental pollution, trigger malignant tumors in the human body.

In the August issue of the journal Nature Medicine, researchers at Thomas Jefferson University in Philadelphia and the University of Naples suggest that a monkey virus may be responsible for the onset of a rare but aggressive form of cancer called mesothelioma.

The results do not prove a causal relationship between simian virus 40, or SV40, and cancer. But researchers say they have evidence of viral proteins from SV40 DNA found in human mesothelioma tumors binding with body proteins that normally suppress tumor growth.

``It's the first time we've identified this mechanism in real human tumors,'' said research leader Dr. Antonio Giordano, a Jefferson Medical College professor and head of the Sbarro Institute for Cancer Research and Molecular Medicine.

``We know that cigarette-smoking is dangerous. We know a virus can cause cancer. We know genetic damage causes cancer. What we need to know is the way these things target different elements in the body. That's the way we're going to diagnose cancer early and, later, how we're going to cure it.''

Cancer researchers have long suspected that viral proteins can trigger cancer growth by shutting down tumor-suppressing proteins made by the body's retinoblastoma, or Rb, genes. Independent medical experts say the latest study would have far-reaching implications for the early diagnosis and treatment of lung, ovarian, breast and cervical cancer if the Giordano team's findings could be reproduced by other laboratories.

``If it's true that SV40 has a causal role in mesolthelioma, then it's of extraordinary importance,'' said Dr. Frederic Kaye, senior clinical investigator for the National Cancer Institute.

Mesothelioma, once thought to be caused solely by exposure to asbestos, attacks the lining of the chest wall and the abdominal cavity. It is diagnosed in 2,000 to 3,000 people a year in the United States. There is no effective treatment.

Three years ago, a group of researchers led by Dr. Michele Carbone of Loyola University discovered DNA from the SV40 virus to be present in mesothelioma patients.

Now, Giordano's team has unearthed evidence that the same viral DNA sequence is producing a protein called SV40 T-ag which in turn is binding with human proteins from the Rb gene.

``This gene is important in all cancers. But what we don't know is the mechanism of other cancers,'' said Giordano, who has been pursuing the same line of cancer research for 10 years.

``In lung cancer, the protein disappears completely. In mesothelioma, the protein is still there but inactive...in breast cancer, the proteins are at normal levels but we don't know why they don't function.''

This fall, the researchers plan to begin clinical tests on several hundred people from the United States, Italy and Austria who have family histories of mesothelioma and lung cancer. Giordano said the team hopes to find clinical data that could be used to enhance early diagnosis and treatment within two years.