同源重组修复对脑胶质瘤替莫唑胺化学敏感性的影响。

IF 3.3 3区 医学 Q2 ONCOLOGY
Biyun Zeng, Hansen Shi, Tiancai Liu, Jinjing Tang, Juncheng Lin, Xiaocong Lin, Tao Zeng
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引用次数: 0

摘要

胶质瘤是原发性脑肿瘤的一种常见形式,替莫唑胺(TMZ)是公认的一线治疗选择。然而,TMZ的有效性受到化学耐药发展的阻碍。最近的研究强调了同源重组修复(HRR)与胶质瘤治疗中TMZ耐药的相关性,HRR是修复DNA双链断裂的关键机制。这篇综述的重点是阐明HRR在胶质瘤治疗中的意义,特别强调HRR过程中涉及的关键分子,包括RAD51、ATM、ATR和新发现的影响HRR的小分子。调节这些基因的表达可有效抑制ATM/CHK2、ATR/CHK1、PI3K/AKT等通路,从而增强胶质瘤对TMZ的敏感性。值得注意的是,在最近的研究中,人们已经在探索这些途径的抑制剂方面做出了努力,最终取得了令人鼓舞的成果。总之,HRR参与胶质瘤耐药揭示了新的治疗途径,靶向HRR通路中的关键分子,有望提高TMZ治疗的有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Influence of Homologous Recombination Repair on Temozolomide Chemosensitivity in Gliomas.

Gliomas represent a prevalent form of primary brain tumors, with temozolomide (TMZ) serving as the established first-line therapeutic option. Nevertheless, the effectiveness of TMZ is hindered by the development of chemoresistance. Recent investigations have underscored the correlation of homologous recombination repair (HRR), a pivotal mechanism responsible for mending DNA double-strand breaks, with TMZ resistance in glioma treatment. This review centers on elucidating the significance of HRR in the management of gliomas, with a particular emphasis on pivotal molecules implicated in the HRR process, including RAD51, ATM, ATR, and newly identified small molecules that impact HRR. Modulating the expression of these genes can effectively restrain pathways such as ATM/CHK2, ATR/CHK1, and PI3K/AKT, subsequently augmenting the sensitivity of gliomas to TMZ. Noteworthy efforts have been directed towards exploring inhibitors of these pathways in recent research endeavors, culminating in encouraging outcomes. In conclusion, the involvement of HRR in glioma resistance unveils novel therapeutic avenues, with targeting crucial molecules in the HRR pathway, holding promise for enhancing the effectiveness of TMZ therapy.

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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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