Reddel Roger R
Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.
Curr Pharm Des. 2014;20(41):6361-74. doi: 10.2174/1381612820666140630101047.
The presence of immortal cell populations with an up-regulated telomere maintenance mechanism (TMM) is an almost universal characteristic of cancers, whereas normal somatic cells are unable to prevent proliferation-associated telomere shortening and have a limited proliferative potential. TMMs and related aspects of telomere structure and function therefore appear to be ideal targets for the development of anticancer therapeutics. Such treatments would be targeted to a specific cancer-related molecular abnormality, and also be broad-spectrum in that they would be expected to be potentially applicable to most cancers. However, the telomere biology of normal and malignant human cells is a relatively young research field with large numbers of unanswered questions, so the optimal design of TMM-targeted therapeutic approaches remains unclear. This review outlines the opportunities and challenges presented by telomeres and TMMs for clinical management of cancer.
具有上调的端粒维持机制(TMM)的永生细胞群体的存在几乎是癌症的普遍特征,而正常体细胞无法阻止与增殖相关的端粒缩短,并且增殖潜力有限。因此,TMM以及端粒结构和功能的相关方面似乎是抗癌治疗药物开发的理想靶点。此类治疗将针对特定的癌症相关分子异常,并且具有广谱性,因为预计它们可能适用于大多数癌症。然而,正常和恶性人类细胞的端粒生物学是一个相对年轻的研究领域,有大量未解决的问题,因此针对TMM的治疗方法的最佳设计仍不明确。本综述概述了端粒和TMM在癌症临床管理中带来的机遇和挑战。