Friday, January 26, 2007

Potential Method of Blocking Cancer Cell Growth Identified

(HealthDay News) -- A new approach that uses small molecules to target cancer cells may be able to disrupt the cells' function and stop them from growing without affecting normal cells, researchers report.

Using these molecules to block other proteins on the cells' surface could lead to future cancer treatments, according to the report in the Jan. 26 issue of Cell.

"We looked for some small molecules that would inhibit the initiation of proteins that cause cancer cells to grow," explained lead researcher Gerhard Wagner, the Elkan Rogers Blout Professor at Harvard Medical School's Department of Biological Chemistry and Molecular Pharmacology.

Most of the growth of cancer cells is governed by so-called "weak" messenger RNAs, which tell the cell what proteins to make. Wagner believes that by exploiting this weakness in cancer cells, scientists can stop these cells from growing. This is done by finding small molecules that can attach themselves to the surface of cancer cells and block the messenger RNAs from communicating with the cells.

"It is a mystery that the genes in cancer are controlled by a group of weak messenger RNAs that shuttle information about how to make proteins," said Gerard I. Evan, the Gerson and Barbara Bass Bakar Distinguished Professor of Cancer Research at the University of California, San Francisco, who was not involved in the study.

Evan said this way of controlling the growth of cancer cells may make them easy to disrupt. It "may be a favor that's been handed to us by evolution, and it may be just a lucky break for human beings in the treatment of disease," he said. "What it means is that it's possible to disrupt the messenger RNAs that are maintaining cancer cells but without disrupting the day-to-day business of the cell."

Wagner's team discovered a small molecule that inhibits the growth of cancer cells but has no effect on the proteins necessary for the functioning of normal cells. The molecule, called 4EGI-1, effectively silences genes that have links to cancer, he said.

For the study, the researchers capitalized on the weakness of cancer-related RNAs by using 4EGI-1 to disrupt the interaction between two proteins, eIF4E and eIF4G.

The researchers then tested their molecule on several types of cancer cells, including leukemia and lung cancer. "We found that these molecules inhibited the growth of these cells and caused them to die," Wagner said. "These compounds are specific for cancer cells, and they have less effect on the growth of non-cancer cells."

This method of preventing the growth of cancer cells may provide new targets for new cancer drugs, Wagner said. "These drugs would work on the principle of inhibiting protein-protein interactions," he said.

Wagner noted that these particular proteins aren't strong enough to be used therapeutically. Before they could play a role in cancer treatment, they would have to be enhanced to have a more powerful impact. Then they would need to be tested in animals before any human trials could occur, he said.

Evan added: "If you accept that the interactions between proteins can be targeted, then it opens up an enormous vista of controlled, targeted therapeutics in all aspects of disease. The ability to disrupt the interface between proteins by a synthetic chemical is very exciting."

Evan added that this approach to drug development could extend beyond cancer. "New technology is going to give us molecules that are designed to fit the shape of proteins we want to disrupt. Then, if you think about what you want to disrupt, well, there's a whole new pharmacology out there," he said.

"The idea is that we can really get to interfering with the bits of cellular processes that we want to interfere with," Evan said. "It's not just about cancer, it's about any pathological situation. Maybe even infectious disease."

More information
The U.S. National Cancer Institute can tell you more about cancer therapy.

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