The University of Texas Southwestern Medical Center, Department of Cell Biology, Dallas, TX 75390-9039, USA.
Mutat Res. 2012 Feb 1;730(1-2):90-7. doi: 10.1016/j.mrfmmm.2011.07.006. Epub 2011 Jul 23.
The ideal cancer treatment would specifically target cancer cells yet have minimal or no adverse effects on normal somatic cells. Telomerase, the ribonucleoprotein reverse transcriptase that maintains the ends of human chromosome, is an attractive cancer therapeutic target for exactly this reason [1]. Telomerase is expressed in more than 85% of cancer cells, making it a nearly universal cancer marker, while the majority of normal somatic cells are telomerase negative. Telomerase activity confers limitless replicative potential to cancer cells, a hallmark of cancer which must be attained for the continued growth that characterizes almost all advanced neoplasms [2]. In this review we will summarize the role of telomeres and telomerase in cancer cells, and how properties of telomerase are being exploited to create targeted cancer therapies including telomerase inhibitors, telomerase-targeted immunotherapies and telomerase-driven virotherapies. A frank and balanced assessment of the current state of telomerase inhibitors with caveats and potential limitations will be included.
理想的癌症治疗方法应该能够特异性地靶向癌细胞，而对正常体细胞的不良影响最小或没有。端粒酶是一种核糖核蛋白逆转录酶，它维持人类染色体的末端，正是由于这个原因，它成为了一种有吸引力的癌症治疗靶点[1]。端粒酶在超过 85%的癌细胞中表达，使其成为几乎普遍的癌症标志物，而大多数正常体细胞都是端粒酶阴性的。端粒酶活性赋予癌细胞无限的复制潜力，这是癌症的一个标志，几乎所有进展性肿瘤的持续生长都必须具备这一特征[2]。在这篇综述中，我们将总结端粒和端粒酶在癌细胞中的作用，以及如何利用端粒酶的特性来创建靶向癌症治疗方法，包括端粒酶抑制剂、端粒酶靶向免疫疗法和端粒酶驱动的病毒疗法。我们将诚实地、平衡地评估端粒酶抑制剂的现状，包括注意事项和潜在的局限性。
