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通过靶向代谢和 DNA 修复途径克服脑胶质瘤的辐射抵抗。

Overcoming Radiation Resistance in Gliomas by Targeting Metabolism and DNA Repair Pathways.

机构信息

Department of Radiation Oncology, The Ohio State University, Columbus, OH 43210, USA.

出版信息

Int J Mol Sci. 2022 Feb 17;23(4):2246. doi: 10.3390/ijms23042246.

Abstract

Gliomas represent a wide spectrum of brain tumors characterized by their high invasiveness, resistance to chemoradiotherapy, and both intratumoral and intertumoral heterogeneity. Recent advances in transomics studies revealed that enormous abnormalities exist in different biological layers of glioma cells, which include genetic/epigenetic alterations, RNA expressions, protein expression/modifications, and metabolic pathways, which provide opportunities for development of novel targeted therapeutic agents for gliomas. Metabolic reprogramming is one of the hallmarks of cancer cells, as well as one of the oldest fields in cancer biology research. Altered cancer cell metabolism not only provides energy and metabolites to support tumor growth, but also mediates the resistance of tumor cells to antitumor therapies. The interactions between cancer metabolism and DNA repair pathways, and the enhancement of radiotherapy sensitivity and assessment of radiation response by modulation of glioma metabolism are discussed herein.

摘要

神经胶质瘤是一组具有广泛生物学特征的脑肿瘤,其特点为高度侵袭性、对放化疗抵抗、肿瘤内和肿瘤间异质性。转录组学研究的最新进展表明,神经胶质瘤细胞的不同生物学层面存在巨大的异常,包括遗传/表观遗传改变、RNA 表达、蛋白质表达/修饰和代谢途径,这为开发新型靶向神经胶质瘤的治疗药物提供了机会。代谢重编程是癌细胞的标志之一,也是癌症生物学研究中最古老的领域之一。癌细胞代谢的改变不仅为肿瘤生长提供能量和代谢物,还介导肿瘤细胞对抗肿瘤治疗的抵抗。本文讨论了癌症代谢与 DNA 修复途径的相互作用,以及通过调节神经胶质瘤代谢增强放疗敏感性和评估放疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5237/8880405/06167cfa05f8/ijms-23-02246-g001.jpg

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