To their surprise, they found that inactivation of ATM kinase prevented a type of DNA repair that is essential for proper duplication of genetic material during replication. However, A-T cells did not have this problem despite lacking the kinase; they presumably use another method to check for and correct those errors.

The discovery revealed a new approach to target cancer.

"A characteristic of tumor cells is that they rapidly replicate, possibly because they have mutations that encourage cell division or that thwart repair pathways," Dr. Bakkenist explained. "But ATM kinase remains present in the vast majority of human cancers, so that suggests it is needed by those diseased cells during replication."

Cells that, unlike cancer cells, are not going through what's known as replication stress, would not be affected by an ATM inhibitor and, like A-T cells, likely have another way of repairing certain radiation-induced mutations, he said.

"So that would make cancer cells particularly vulnerable to an ATM inhibitor, while healthy cells should be unaffected," Dr. Bakkenist said.

He and his team are now studying the effects of such inhibitors on pancreatic, lung and breast cancer cells.

Source: University of Pittsburgh Schools of the Health Sciences