Blocking Telomerase Remortalizes Cancer Cells - Brief Article

Applied Genetics News, Dec 19, 1999

B.-S. Herbert, A. E. Pitts, and colleagues at the University of Texas Southwestern Medical Center (5323 Harry Hines Blvd., Dallas, TX 75235) have shown that inhibitors of telomerase can remortalize transformed human breast epithelial cells and human prostate cancer cells in culture, ultimately leading to their cell death. The research, published in the December 7, 1999 issue of the Proceedings of the National Academy of Sciences, was funded in part by Geron Corp. (230 Constitution Dr., Menlo Park, CA 94025; Tel: 650/473-7700, Fax: 650/473-7701) and the National Institutes of Health. Geron cloned the gene for human telomerase in 1994 and published the first evidence of specific telomerase inhibition leading to tumor cell death in 1995.

Telomeres, the regions at the ends of chromosomes, shorten throughout a cell's replicative lifespan. When telomeres reach a critically short length, cells stop dividing and senesce. Geron and collaborating researchers have shown that malignant cells achieve replicative immortality through telomerase activation. Telomerase activity is detectable in over 30 different human cancer types, although by itself, telomerase activity is insufficient to render a cell tumorigenic.

The telomerase inhibitors used in this study were 2'-0-MeRNA oligonucleotides directed towards the essential RNA component (hTR) of human telomerase. Telomere shortening was reversible: if inhibitor addition is terminated, telomeres regain their initial lengths. According to Burke and Pitts, oligonucleotides chemically similar to theirs are in clinical trials and have well- characterized pharmacokinetics. Therefore, the telomerase inhibitors they describe are practical lead compounds for testing for an anti-telomerase chemotherapeutic strategy.