Reduced Telomerase Activity Slows Development of Several Common Cancers

Inhibition of the enzyme telomerase, which is overexpressed in most human cancers, may be the method of choice for treating several common carcinomas, including breast, lung, liver, and gastrointestinal cancers.

Telomerase is activated in most human cancers and is critical for cancer cell growth. However, little was known about the significance of telomerase activation in chromosome instability and cancer initiation.

Investigators at Harvard University Medical School (Boston, MA, USA) have been studying the role of the telomerase inhibitor PinX1 (PIN2/TRF1-interacting, telomerase inhibitor 1) in the metabolic processes that lead to cancer formation.

They reported in the March 23, 2011, online edition of the Journal of Clinical Investigation that reduced PinX1 activity contributed to cancer development in a mouse population that had been genetically engineered to lack one allele of the PinX1 gene. Reduced PinX1 activity in cells of these animals not only caused telomerase activation, it also triggered chromosome instability. Most of the PinX1 mutant mice spontaneously developed carcinomas.

"Although telomerase is activated in 85% to 90% of human cancers, little has been known about the significance of telomerase activation in chromosome instability and cancer initiation,” explained senior author Dr. Kun Ping Lu professor of medicine at Harvard Medical School. "We have discovered, for the first time, a novel role for abnormal telomerase activation in cancer initiation. This suggests that telomerase inhibition using PinX1 or other small molecules may be used to treat certain cancers with activated telomerase.”

"Going forward, we are also interested in determining the genetic changes that underlie PinX1 reduction in cancers,” said Dr. Lu. "This might lead to new diagnostic tools to better identify individuals who are susceptible to certain cancers, and therefore, might be suitable for treatment with telomerase inhibitors.”

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