Their findings appear in the current issue of the journal Cancer Research.

The researchers sought to inhibit telomerase, an enzyme that maintains telomeres repeating sequences of DNA at the end of each chromosome that are believed to function as a counting mechanism for cellular aging. Telomerase prevents the shortening of the sequences of DNA that occurs in normal cells as they age. The enzyme is found in most types of tumor cells but not healthy cells, indicating telomerase inhibitors may be a powerful new approach to chemotherapy.

Telomerase inhibition, however, has posed challenges for therapy. In earlier studies, scientists have found that months of treatment with an inhibitor are required before tumor growth could be expected to significantly slow.

The UT Southwestern researchers treated cultured human tumor cells with a unique compound that blocks telomerase activity, and the cell proliferation slowed substantially after just a few weeks.

Further, prostate cancer cells treated with the inhibitor barely formed tumors in mice and yielded very low levels of prostate specific antigen (PSA), a marker associated with malignancy. Cells treated with a similar compound that was not a telomerase inhibitor formed large tumors with high PSA levels.

"Telomerase is widely appreciated as a promising target for therapy," said Dr. David Corey, professor of pharmacology and biochemistry and the study's senior author. "Our results suggest that if you can inhibit telomerase in tumor cells and shorten telomeres, you will slow the growth of tumors."

The researchers also discovered that when the telomerase inhibitor is combined with standard cancer therapeutic agents carboplatin and cisplatin
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Contact: Scott Maier
scott.maier@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
15-Sep-2003