Often likened to the plastic tips on shoelaces that prevent their unraveling, telomeres are molecular structures that cap the ends of chromosomes in cells and protect their DNA from damage. Chromosomes are the rod-like structures that contain the genes and other DNA in cells.
Telomeres gradually shorten every time a cell divides, however, resulting in less protection for the chromosomes. After a certain number of divisions, one of two things happens:
- The chromosomes become damaged and genetically unstable to the point that the cells can’t divide any more — a state called senescence.
- The cells trigger a self-destruct program, known as apoptosis, ending the life of the cell.
Ultimately, telomeres play a direct role in a person’s biological clock of aging.
How do telomeres play a role in cancer?
Cancer cells often avoid senescence or cell death by maintaining their telomeres despite repeated cell divisions. This is possible because the cancer cells activate an enzyme called telomerase, which adds genetic units onto the telomeres to prevent them from shortening to the point of causing senescence or cell death.
Telomerase is silenced in most normal cells but is active in an estimated 85% to 95% of human cancer cells. As a result, cancer cells essentially become immortal. For this reason, some have called telomerase the “immortality enzyme.” Nevertheless, the telomeres in cancer cells are generally shorter than telomeres in normal cells.
Since telomerase is active in cancer cells but not normal cells, it is seen as a promising target for cancer therapy. Due to telomerase inhibition, activity, or expression, targeted drugs might kill tumor cells by allowing telomeres to shrink or by provoking apoptosis. To that end, scientists have been investigating what genes and other factors are involved in activating telomerase in cancer cells, so that strategies can be developed to suppress telomerase in tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control.
Development of telomerase inhibitors has proved challenging. Various methods for targeting telomerase have been investigated, including cancer vaccines, immunotherapy, and small-molecule inhibitors. At present, there are no clinically approved strategies exploiting telomerase as a cancer therapy target.