Telomerase is a protein that protects chromosome integrity by adding small pieces of DNA nucleotides to the ends of chromosomes. Importantly, telomerase is expressed in 90 percent of cancers, but not or only transiently expressed in normal cells, making this protein an effective, universal and specific therapeutic target in the fight against cancer.
Cell division and Telomerase
During normal growth, repair and maintenance, cell division is required where the entire cell and its components are effectively duplicated. When chromosomes from the cell replicate, specialized structures at the end of linear chromosomes, telomeres, consisting of specific DNA repeats, break off. The cell fixes these breaks in DNA and prevents the activation of programmed cell death that may eventually result from the cell sensing non-repaired DNA. After each replication, these telomeric DNA repeats get shorter, but when telomeres become too short, cells reach the Hayflick limit. This is the number of times a normal cell population will divide before it stops. Cell division is therefore limited. Telomerase can fix the telomeres by replacing lost pieces of DNA. Research by Carmela Morales et al., published in a letter to "Nature Genetics" in 1999 showed that introduction of telomerase into human cells causes cells to start dividing again and extended their lifespan.
Telomerase and Cancer
Uncontrolled cell division leads to excessive growth and potentially cancer. The heightened telomerase activity shown in many different tumor types enables cancer cells to maintain telomere length, providing them with a continuous replicating capacity. Additionally, inhibiting telomerase activity to prevent telomere elongation leads to cell division and promote cell death in several tumor models, causing telomere shortening and death of cancer cells.
A Therapeutic Target
Imetelstat is a drug that binds with high affinity to a specific region to telomerase and inhibits its activity. Six Phase 1 clinical trials at 22 U.S. medical centers treating more than 180 patients used imetelstat, and the studies showed that the drug was safe and had met the standards for tolerability and safety. GRNVAC1 also was found to be safe in a 2009 trial performed on 31 patients with acute myelogenous leukemia.
Conclusion
Since telomerase is predominantly expressed in cancer cells, therapies targeting this protein would be safe as it would not affect normal cells. This approach by itself, or in conjunction with other current cancer therapeutics is under way and shows promise; however, such clinical trials are still in the early phases. Furthermore, potential side effects after long-term use will have to be evaluated.
