There are plenty of cancer therapies already on the market. The trick, as any cancer specialist will tell you, is finding treatments that can target tumors without taking out too many healthy cells in the process. Dr. Maria Laura Avantiaggiati, assistant professor of pharmacology, may be on the molecular trail of one such therapy.

As a continuation of work she has performed at the National Institutes of Health (NIH), Dr. Avantiaggiati's laboratory at GW is working with a family of specific enzymes, especially a protein known as p300. In short, p300 appears to slow the unrestrained growth found in tumors
by kick-starting another key protein, p53, into action.

In normal cells, p53 acts as a kind of enforcer of proper growth by killing off cells with irreparable DNA damage. “This p53-mediated cell death, also called apoptosis, represents a self-defense mechanism that is activated in normal tissues to eliminate ‘bad' cells,” said Dr. Avantiaggiati, “particularly those that have acquired the capability to grow indefinitely.”

Most tumor cells have mutations in the p53 gene that keep it from doing its job. But Dr. Avantiaggiati has discovered that introducing fragments of p300 and another closely related protein known as P/CAF into these cells can restore normal p53 function, effectively sounding the death knell for the tumor cells.

“Because of its important role in provoking cell death, p53 has represented for many years one of the most rewarding and attractive targets for drug intervention,” said Dr. Avantiaggiati. Her work is currently taking place in mouse models, but she says this is groundwork for an eventual treatment for humans.

More generally, Dr. Avantiaggiati says a p53 treatment may one day be part of an emerging menu of therapies designed to treat cancer as more of a long-term disease.

“We may be shifting from a very aggressive type of chemotherapy —i.e., high doses in short periods of time—to Maria Avantiaggiati, MD something more subtle. Chemotherapy may be administered continuously, but at lower doses with devices such as pumps, that allow continuous infusion and resemble those used in diabetic patients,” she said. “The idea of making cancer a chronic disease has proven successful in a number of clinical trials.”

- Reprinted with permission from Progress , March 2003