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细胞代谢与DNA修复途径:对癌症治疗的启示

Cell Metabolism and DNA Repair Pathways: Implications for Cancer Therapy.

作者信息

Sobanski Thais, Rose Maddison, Suraweera Amila, O'Byrne Kenneth, Richard Derek J, Bolderson Emma

机构信息

Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, Australia.

Princess Alexandra Hospital, Brisbane, QLD, Australia.

出版信息

Front Cell Dev Biol. 2021 Mar 23;9:633305. doi: 10.3389/fcell.2021.633305. eCollection 2021.

Abstract

DNA repair and metabolic pathways are vital to maintain cellular homeostasis in normal human cells. Both of these pathways, however, undergo extensive changes during tumorigenesis, including modifications that promote rapid growth, genetic heterogeneity, and survival. While these two areas of research have remained relatively distinct, there is growing evidence that the pathways are interdependent and intrinsically linked. Therapeutic interventions that target metabolism or DNA repair systems have entered clinical practice in recent years, highlighting the potential of targeting these pathways in cancer. Further exploration of the links between metabolic and DNA repair pathways may open new therapeutic avenues in the future. Here, we discuss the dependence of DNA repair processes upon cellular metabolism; including the production of nucleotides required for repair, the necessity of metabolic pathways for the chromatin remodeling required for DNA repair, and the ways in which metabolism itself can induce and prevent DNA damage. We will also discuss the roles of metabolic proteins in DNA repair and, conversely, how DNA repair proteins can impact upon cell metabolism. Finally, we will discuss how further research may open therapeutic avenues in the treatment of cancer.

摘要

DNA修复和代谢途径对于维持正常人类细胞的细胞稳态至关重要。然而,在肿瘤发生过程中,这两种途径都会发生广泛变化,包括促进快速生长、遗传异质性和存活的修饰。虽然这两个研究领域相对独立,但越来越多的证据表明这些途径相互依存且内在相连。近年来,针对代谢或DNA修复系统的治疗干预已进入临床实践,凸显了在癌症中靶向这些途径的潜力。进一步探索代谢途径与DNA修复途径之间的联系可能会在未来开辟新的治疗途径。在此,我们讨论DNA修复过程对细胞代谢的依赖性;包括修复所需核苷酸的产生、DNA修复所需染色质重塑的代谢途径的必要性,以及代谢本身诱导和预防DNA损伤的方式。我们还将讨论代谢蛋白在DNA修复中的作用,反之,DNA修复蛋白如何影响细胞代谢。最后,我们将讨论进一步的研究如何在癌症治疗中开辟治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dc4/8021863/d4f72161cd01/fcell-09-633305-g001.jpg

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