Certain enzyme inhibitors can slow tumor formation in cultured human tumor cells within weeks of first exposure and may lead to treatments to delay or prevent recurrent cancer, according to an article in the September issue of Cancer Research.

In the current work, American researchers studied inhibition of telomerase, an enzyme that maintains chromosomal telomeres, structures that are believed to function as a counting mechanism for cellular aging. Telomerase prevents the shortening of DNA sequences that occurs in normal cells as they age. The enzyme is found in most types of tumor cells but not in healthy cells, which suggested to the researchers that telomerase inhibitors may be a powerful new approach to therapy.

In earlier studies, scientists found that months of treatment with an inhibitor are required before tumor growth could be expected to significantly decrease; however, the researchers in the current work treated cultured human tumor cells with a unique compound that blocks telomerase activity, and cell proliferation slowed substantially after just a few weeks.

Furthermore, prostate cancer cells treated with the inhibitor barely formed tumors in mice and yielded very low levels of prostate specific antigen. Prostate cancer cells treated with a similar compound that was not a functional telomerase inhibitor formed large tumors in mice and yielded high antigen levels.

“Telomerase is widely appreciated as a promising target for therapy,” said Dr. David Corey, 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 their telomerase inhibitor is combined with carboplatin and cisplatin, there are additional antiproliferative effects. Corey said these results suggest a relatively small amount of telomere shortening is sufficient to slow tumor growth, and telomerase inhibitors are a useful therapeutic option, especially in combination with agents already in use to treat patients.

“No one is suggesting telomerase inhibitors alone would cure cancer, but in conjunction with standard therapy, they might help to slow or prevent the recurrence of tumors after the initial cancer has been removed through surgery, radiation, or chemotherapy,” Corey said. “Since most patients die from the recurrence of cancer, effective telomerase inhibitors could have a large impact on the treatment of many different types of cancer.”

A similar telomerase inhibitor currently is in advanced preclinical trials with a private corporation. Corey said that his group’s new findings are likely to influence the design of clinical trials and provide additional support for their initiation.