Exploiting Cancer’s Achilles’ Heel

Could the ability of cancer cells to quickly alter their genome be used as a weapon against malignant tumors? Researchers at Uppsala University have succeeded in developing a substance that has demonstrated promising results in experiments on both animal models and human cancer cells. The study was published today in the journal Nature Communications.

Typically, cancer cells are able to quickly alter their DNA; however, in their haste to acquire new mutations, they carelessly discard many of their inherited genetic variations. This may lead to cancer cells only retaining a defective allele of a gene from one parent, whereas healthy cells also have a functioning allele from the other parent. This characteristic of cancer cells may well be an Achilles’ heel that can be exploited in the development of new drugs.

“We searched for genes of which many people carry both a functioning and defective allele in their DNA,” explains senior author Tobias Sjöblom of Uppsala University’s Department of Immunology, Genetics and Pathology. “One such gene, NAT2, produces a protein that metabolizes a number of drugs and is of particular interest, as one allele is often lost during the development of colon and rectal cancer.”

Based on their discovery, the researchers developed a substance that kills cells lacking NAT2. They were able to demonstrate that their drug can be used to treat both animal models of cancer and tumor cells from patients.

“The conditions for treatment exist in 50,000 of the colorectal cancer patients diagnosed globally each year, and we will, therefore, continue working to identify substances with even better properties for pharmaceutical development,” Sjöblom says.