By tapping into a cell's natural processes, researchers may have found a way to inhibit tumor growth and ultimately kill off cancer cells.
Cells have "biological clocks" defined by telomeres, or the DNA structures capping off the ends of chromosomes for protection against damage. Each time a cell divides, telomeres shorten. When they reach a certain length, the cell is informed that it can no longer divide, prompting death through a process called apoptosis.
Unfortunately, telomerase, an RNA protein complex, protects cancer cells from apoptosis. By ensuring telomeres maintain their length even with division, telomerase lets cancer cells evade natural cell death.
A small molecule, 6-thio-2'-deoxyguanosine acts by regulating the function of telomeres. As it is used by telomerase as a substrate, 6-thiodG disrupts the manner by which cells maintain the length of their telomeres. The molecule is not normally used by telomeres, so the cell will recognize its presence as "damage," prompting the cell to stop dividing and die.
Other drugs have been developed to block the action of telomerase, but these have to be taken by patients for long periods of time to shrink tumors and successfully trigger death in cancer cells. One of the reasons for this is that telomeres vary in length, so cancer cells die at varying rates.
Telomerase is a popular oncology target but few human clinical trials are focused toward taking advantage of telomerase-directed treatments.
"We believe this small molecule will address an unmet cancer need in an underexplored area that will be rapidly applicable to the clinic," said Dr. Jerry Shay, vice-chairman and professor of cell biology at the University of Texas Southwestern Medical Center and senior co-author for the study.
The use of 6-thiodG in place of other compounds that inhibit telomerase was also observed by researchers to be lacking serious side effects in the kidneys, blood and liver of mice test subjects.
The study, published in the journal Cancer Discovery, received funding support from the National Cancer Institute's Specialized Program of Research Excellence grant, the Southland Financial Corporation Distinguished Chair in Geriatric Research and the Harold C. Simmons Comprehensive Cancer Center.
Other authors of the study include Dr. Woodring Wright from UT Southwestern; Sergei Gryaznov from AuraSense Therapeutics in Illinois; Z. Gunnur Dikmen from the Hacettepe University in Turkey; and Ilgen Mender, a visiting junior researcher in UT Southwestern's Department of Cell Biology from Hacettepe University.
