Researchers at the University of Rochester have designed a gene that produces a thousand times more protein in cancer cells than in healthy cells.

The findings may help address the prime challenge in anti-cancer therapy: improving treatments' ability to specifically and effectively target cancer cells. Using this new approach, scientists should be able to insert "self-destruct" codes into the modified gene, forcing cancer cells to kill themselves while healthy cells remain largely unaffected.

Though trials will be necessary to determine if the difference is enough to destroy tumors without harming healthy tissue, the initial findings, published on Wednesday's Proceedings of the National Academy of Sciences, are promising, say the researchers.

They were investigating Rad51, a protein that is expressed at about five times higher level in cancer cells than in healthy cells, when they stumbled on something very unexpected.

"We stripped off some of the Rad51 gene and replaced it with a marker protein DNA to see why Rad51 was five times more abundant in cancer cells," says lead researcher Vera Gorbunova. "We wanted to see if there was any way we could boost that difference and create a really useful cancer-targeting tool. We couldn't believe it when we saw the cancer cells expressing the engineered Rad51 around a thousand times more."

Further tests showed that the altered Rad51 was expressed in some cancer cells as much as 12,500 times as often as healthy cells. Such a large discrepancy means scientists should be able to use it to create versions of Rad51 that carry a "toxic bomb," which only the cancer cells will trigger.

Gorbunova and her team have already fused a variant of diphtheria toxin into the Rad51 gene as a "toxic bomb" and tested it on a variety of cancer cell types, including breast cancer and cervical cancer cells. The results look very promising, she says.

If the further tests on animals are successful, Gorbunova hopes the process might be someday given as a simple shot-in-the-arm, which might travel throughout the bloodstream and stop metastasis in its tracks.

(Xinhua News Agency December 18, 2008)