文章：

靶向端粒：端粒维持机制特异性癌症治疗的进展

Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies

原文发布日期：2022-07-05

DOI: 10.1038/s41568-022-00490-1

类型: Review Article

开放获取: 否

英文摘要：

Cancer cells establish replicative immortality by activating a telomere-maintenance mechanism (TMM), be it telomerase or the alternative lengthening of telomeres (ALT) pathway. Targeting telomere maintenance represents an intriguing opportunity to treat the vast majority of all cancer types. Whilst telomerase inhibitors have historically been heralded as promising anticancer agents, the reality has been more challenging, and there are currently no therapeutic options for cancer types that use ALT despite their aggressive nature and poor prognosis. In this Review, we discuss the mechanistic differences between telomere maintenance by telomerase and ALT, the current methods used to detect each mechanism, the utility of these tests for clinical diagnosis, and recent developments in the therapeutic strategies being employed to target both telomerase and ALT. We present notable developments in repurposing established therapeutic agents and new avenues that are emerging to target cancer types according to which TMM they employ. These opportunities extend beyond inhibition of telomere maintenance, by finding and exploiting inherent weaknesses in the telomeres themselves to trigger rapid cellular effects that lead to cell death.

摘要翻译： 

癌细胞通过激活端粒维持机制（无论是端粒酶还是端粒替代延长途径）获得复制永生性。靶向端粒维持机制为治疗绝大多数癌症类型提供了诱人机遇。虽然端粒酶抑制剂历来被誉为有前景的抗癌药物，但实际应用面临更多挑战，且目前对使用ALT途径的侵袭性强、预后差的癌症类型尚无治疗选择。本综述将探讨端粒酶与ALT维持端粒的机制差异、现有检测方法及其临床诊断价值，以及针对这两种机制的最新治疗策略进展。我们重点介绍了成熟治疗药物再利用的重要进展，以及根据癌细胞采用的特定端粒维持机制进行靶向治疗的新途径。这些机遇不仅限于抑制端粒维持功能，更包括发现并利用端粒自身固有弱点以触发导致细胞死亡的快速细胞效应。

原文链接：

Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies