Silvia Siteni1,2, Anthony Grichuk1,2 and Jerry W. Shay1 1University of Texas Southwestern Medical Center, Department of Cell Biology, Dallas, Texas 75390, USA Correspondence: jerry.shayutsouthwestern.edu

↵2 These authors contributed equally to this work.

While silent in normal differentiated human tissues, telomerase is reactivated in most human cancers. Thus, telomerase is an almost universal oncology target. This update describes preclinical and clinical advancements using a variety of approaches to target telomerase. These include direct telomerase inhibitors, G-quadruplex DNA-interacting ligands, telomerase-based vaccine platforms, telomerase promoter-driven attenuated viruses, and telomerase-mediated telomere targeting approaches. While imetelstat has been recently approved by the Food and Drug Administration (FDA), several other approaches are in late-stage clinical development. The pros and cons of the major approaches will be reviewed.