Siteni Silvia, Grichuk Anthony, Shay Jerry W
University of Texas Southwestern Medical Center, Department of Cell Biology, Dallas, Texas 75390, USA
University of Texas Southwestern Medical Center, Department of Cell Biology, Dallas, Texas 75390, USA.
Cold Spring Harb Perspect Biol. 2024 Dec 2;16(12):a041703. doi: 10.1101/cshperspect.a041703.
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.
端粒酶在正常分化的人体组织中不表达，但在大多数人类癌症中会重新激活。因此，端粒酶几乎是一个通用的肿瘤学靶点。本综述介绍了使用多种靶向端粒酶方法的临床前和临床进展。这些方法包括直接端粒酶抑制剂、与G-四链体DNA相互作用的配体、基于端粒酶的疫苗平台、端粒酶启动子驱动的减毒病毒，以及端粒酶介导的端粒靶向方法。虽然艾美拉唑最近已获得美国食品药品监督管理局（FDA）的批准，但其他几种方法正处于临床后期开发阶段。本文将对主要方法的优缺点进行综述。
