Modified DNA May Be the Key to Targeted Anti-Cancer Therapy

Cancer researchers have capitalized on the huge difference in Rad51 gene expression between normal and cancer cells to design a drug to kill tumors with minimal effect on normal tissues.

Investigators at the University of Rochester (NY, USA) had been studying Rad51 and its protein, which is overexpressed in a variety of tumors and indicative of a poor prognosis. The Rad51 protein is involved in repair of DNA damage and is usually about five to six times more prevalent in cancer cells than in normal tissue.

In the current study, the investigators modified the Rad51 gene and replaced part of it with a special biomarker. They reported in the December 23, 2008, online edition of Proceedings of the [U.S.] National Academy of Sciences (PNAS) that the modified Rad51 gene behaved in a very unexpected fashion. By modifying the Rad51 DNA they had apparently removed some regulatory elements, which caused Rad51 protein to be expressed by as much as 12,500 times the amount found in normal cells.

The investigators then linked the modified Rad51 gene to the gene that produces diphtheria toxin. They found that the resulting toxic protein could effectively kill a variety of cancer cell types, including breast cancer, fibrosarcoma, and cervical cancer cells while having minimal effect on normal breast epithelial cells and normal fibroblasts.

"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," explained senior author Dr. Vera Gorbunova, assistant professor of biology at the University of Rochester. "We wanted to see if there was any way we could boost that difference and create a really useful cancer-targeting tool. We could not believe it when we saw the cancer cells expressing the engineered Rad51 around a thousand times more. The early results show the new Rad51 killed all of the cancer cells with minimal if any effect on normal cells. We are very excited. The results are much more striking than anything we would have guessed."

Related Links:
University of Rochester