Telomerase

The maintenance of telomeres by the cellular ribonucleoprotein enzyme telomerase is of well-documented importance for cancer. Telomerase, a cellular reverse transcriptase that adds DNA to the ends of chromosomes, is reactivated or upregulated in the vast majority of advanced malignancies, and is thus an almost universal target for the treatment of human cancers. Most human tumors not only express telomerase but also have very short telomeres, whereas telomerase activity is absent or at lower levels in normal tissues which also have longer telomeres. This relationship between activation of telomerase activity and short telomeres in human malignancies makes the inhibition of telomerase a valuable target for cancer therapeutics. Importantly, the mode of action of telomerase inhibitors predicts minimal side effects on normal stem cells that can express telomerase. In summary, the growing literature of studies on human telomeres and telomerase highlights the complex interplay between signals emanating from dysfunctional telomeres and tumor suppressor pathways that regulate stem cell biology and how this may relate to both aging and cancer. A more complete understanding of these relationships should lead to more effective clinical trials.