Stewart Sheila A, Hahn William C
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Curr Cancer Drug Targets. 2002 Mar;2(1):1-17. doi: 10.2174/1568009023334015.
The maintenance of specialized nucleoprotein structures at the ends of human chromosomes called telomeres is essential for chromosome stability, and plays a fundamental role in the regulation of cellular lifespan. Without new synthesis of telomeres, chromosome ends shorten with progressive cell division, eventually triggering either replicative senescence or apoptosis when telomere length becomes critically short. The regulation of telomerase activity in human cells plays a significant role in the development of cancer. Telomerase is tightly repressed in the vast majority of normal human somatic cells but becomes activated during cell immortalization and in cancers. Recent work has demonstrated that inhibiting or targeting telomerase shows promise as a novel anti-neoplastic strategy; however, the biology of telomeres and telomerase predict that such approaches will differ in important ways from traditional cytotoxic drug therapies. Understanding telomerase biology may eventually lead to several types of clinically effective, telomerase-based therapies for neoplastic disease.
在人类染色体末端维持称为端粒的特殊核蛋白结构对于染色体稳定性至关重要，并在细胞寿命调节中发挥着基本作用。如果没有端粒的新合成，染色体末端会随着细胞的不断分裂而缩短，当端粒长度变得极短时，最终会触发复制性衰老或细胞凋亡。人类细胞中端粒酶活性的调节在癌症发展中起着重要作用。端粒酶在绝大多数正常人类体细胞中受到严格抑制，但在细胞永生化过程和癌症中会被激活。最近的研究表明，抑制或靶向端粒酶有望成为一种新型抗肿瘤策略；然而，端粒和端粒酶的生物学特性预示着这些方法在重要方面将与传统的细胞毒性药物疗法有所不同。了解端粒酶生物学最终可能会带来几种针对肿瘤疾病的基于端粒酶的临床有效疗法。
