Telomerase: Target for cancer treatment

Introduction Telomerase, a cellular reverse transcriptase that adds DNA to the ends of chromosomes, is reactivated or up-regulated in the vast majority of human advanced malignancies, and is thus an almost universal target for human cancer. 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 novel target for cancer therapeutics. Importantly, the mode of action of telomerase inhibitors predicts minimal side effects on normal stem cells that can express telomerase. Here we summarize the role of telomeres and telomerase in cancer and review the current status of ongoing telomerase clinical trials. This chapter will also discuss the relationship of telomerase to cancer stem cells. Central questions remaining include: What are the key safety concerns, such as the effect of telomerase inhibitors on normal stem cells that express some telomerase? Do cancer stem cells express telomerase activity? What effect will telomerase inhibitors have if cancer stem cells are more quiescent than the bulk of the more differentiated tumor cells? Will human cancers become resistant to telomerase inhibitors?