Jefferson Scientists Suppress Tumor Growth In Animals, Aiming At Gene Therapy

Scientists at Jefferson Medical College believe they have taken the next step toward gene therapy trials for lung cancer. They have demonstrated for the first time in laboratory animals that a normally protective anticancer gene, pRb2/p130, can actually block tumors from growing. A damaged version of the gene, termed a "tumor suppressor," has been implicated in several cancers, such as lung, breast and endometrial.

Previous test tube experiments had proven that tumors wouldn't grow when the gene--and its protein product--were present. But 'curing cancer' in the test tube is one thing. Now that they've found the gene stops cancer formation in an animal model, the next step would be to understand how the gene and its protein actually work. Eventually, the scientists, led by Antonio Giordano, M.D., Ph.D., associate professor of pathology, anatomy and cell biology at Thomas Jefferson University in Philadelphia, would like to develop a gene therapy procedure against Rb2 to treat cancer.

Verifying Rb2's function, Dr. Giordano says, "shows the complexity of cancer. It's clear that Rb2 is one of a small number of tumor suppressor genes that play important roles in cancer," he says. "We know now that Rb2 can be therapeutically powerful. Understanding how they work is key to solving the puzzle of cancer formation. We think that Rb2 is used in combination with other tumor suppressor genes."

Dr. Giordano and his colleagues at Allegheny University of the Health Sciences and the University of Naples report their results October 7 in the Journal of the National Cancer Institute. "The importance of this work is that it's the first time we have shown that the tumor suppressor, pRb2/p130, is able to suppress tumor growth in mice," says Dr. Giordano. "In the past, we only showed that Rb2 could suppress cancer cell lines from growing. Now we find it dramatically does so on mice. It's a very exciting study to show this dramatically inhibiting cancer cell growth."

While the biochemical pathway of tumor suppression isn't completely understood, "with this discovery, we have another tool," Dr. Giordano says. "It's known that Rb2 controls vital cell processes, including apoptosis (programmed cell death). Gene therapy would target cancers in which we know this gene is involved--lung, mesothelioma, endometrial, breast, glioblastoma, lymphoma," he says. "We are working on a delivery system for every cancer."