HHMI scientists at the University of Texas Southwestern Medical Center are blocking the enzyme telomerase in a new strategy to prevent cancer cells from dividing.

Hughes scientists at the University of Texas Southwestern Medical Center have devised a new strategy to prevent cancer cells from dividing.

In the May 1996 issue of Nature Biotechnology , they show that a chemical compound sticks to and blocks an enzyme that may be necessary for the growth of human tumors.

The enzyme, telomerase, is thought to be responsible for maintaining the length of chromosomes. As normal cells divide, the tip of the chromosome, or telomere, becomes shorter with each division. Ultimately, telomeres become so short that a cell can no longer divide and the cell line dies. Normal cells have a finite life span as opposed to cancer cells, which are "immortal."

One controversial theory suggests that cancer cells achieve their immortality because telomerase does not allow the telomere to wear down. This work stems from research by Jerry Shay and Woodring Wright of UT Southwestern, who collaborated with HHMI investigator David R. Corey on the Nature Biotechnology paper. (Shay and Wright demonstrated that telomerase is present in most cancer cells, but not in normal cells.) "As a result, we believe that if you block telomerase activity, over time you may be able to prevent cancer cells from dividing," said Corey.

A chemist by training, Corey has exploited a new class of chemicals called peptide nucleic acids (PNAs) that pair with DNA and RNA to achieve a variety of goals. "PNAs are very attractive as potential drugs because they are highly selective as to where they bind and also because they bind tightly to the targeted molecule," Corey said. "Telomerase was an ideal target for PNAs because it has an RNA component." In the paper, Corey's team demonstrated that relatively small amounts of PNAs could bind to and inhibit the function of telomerase.

"This gives us the potential to target an enzyme that may be very important in cancer cell growth and to cause the cell to stop dividing," Corey said. Further work will be needed to determine whether blocking telomerase activity will kill cells. Corey said his team also plans to engineer PNAs that will cross cell membranes, a stumbling block that must be overcome if PNAs are to be used therapeutically.