Small Molecule Used to Inhibit Telomerase in Cancer-Fighting Effort; Rapid Application to Clinic May Be Possible; “Remarkably Encouraging” Results

Cell biologists at the University of Texas (UT) Southwestern Medical Center have targeted telomeres (see image) with a small molecule called 6-thiodG that takes advantage of the cell's “biological clock” to kill cancer cells and shrink tumor growth. Dr. Jerry W. Shay, Professor and Vice Chairman of Cell Biology at UT Southwestern, and colleague, Dr. Woodring E. Wright, Professor of Cell Biology and Internal Medicine, found that 6-thio-2'-deoxyguanosine (6-thiodG) could stop the growth of cancer cells in culture and decrease the growth of tumors in mice. "We observed broad efficacy against a range of cancer cell lines with very low concentrations of 6-thiodG, as well as tumor burden shrinkage in mice," said Dr. Shay, Associate Director of the Harold C. Simmons Comprehensive Cancer Center. Dr. Shay and Dr. Wright, who hold The Southland Financial Corporation Distinguished Chair in Geriatrics, are co-senior authors of the paper published online on December 16, 2014 in Cancer Discovery. 6-thiodG acts by targeting a unique mechanism that is thought to regulate how long cells can stay alive, a type of aging clock. This biological clock is defined by DNA structures known as telomeres, which cap the ends of the cell's chromosomes to protect them from damage, and which become shorter every time the cell divides. Once telomeres have shortened to a critical length, the cell can no longer divide and dies though a process known as apoptosis. Cancer cells are protected from this death by an RNA protein complex called telomerase, an enzyme that ensures that telomeres do not shorten with every division. Telomerase has therefore been the subject of intense research as a target for cancer therapy.
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