Highlighting vulnerabilities in the alternative lengthening of telomeres pathway

IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Current Opinion in Pharmacology Pub Date : 2023-06-01 DOI:10.1016/j.coph.2023.102380
Lisa M. Carson, Rachel L. Flynn
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引用次数: 1

Abstract

The alternative lengthening of telomeres (ALT) pathway is a telomere elongation mechanism found in a small but often aggressive subset of cancers. Dependent on break-induced replication, telomere extension in ALT-positive cells relies on a baseline level of DNA replication stress to initiate elongation events. This results in an elevated level of DNA damage and presents a possible vulnerability to be exploited in the development of ALT-targeted cancer therapies. Currently, there are no treatment options that target the ALT mechanism or that are specific for ALT-positive tumors. Here, we review recent developments and promising directions in the development of ALT-targeted therapeutics, many of which involve tipping the balance towards inhibition or exacerbation of ALT activity to selectively target these cells.

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强调端粒替代延长途径的脆弱性
端粒选择性延长(ALT)途径是一种端粒延长机制,在一小部分但往往具有侵袭性的癌症中发现。ALT阳性细胞的端粒延长依赖于断裂诱导的复制,依赖于DNA复制应激的基线水平来启动延长事件。这导致DNA损伤水平升高,并可能在ALT靶向癌症疗法的开发中被利用。目前,还没有针对ALT机制或ALT阳性肿瘤的特异性治疗方案。在这里,我们回顾了ALT靶向疗法的最新发展和有希望的发展方向,其中许多涉及将平衡转向ALT活性的抑制或恶化,以选择性地靶向这些细胞。
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来源期刊
CiteScore
8.80
自引率
2.50%
发文量
131
审稿时长
4-8 weeks
期刊介绍: Current Opinion in Pharmacology (COPHAR) publishes authoritative, comprehensive, and systematic reviews. COPHAR helps specialists keep up to date with a clear and readable synthesis on current advances in pharmacology and drug discovery. Expert authors annotate the most interesting papers from the expanding volume of information published today, saving valuable time and giving the reader insight on areas of importance.
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