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引用次数: 0
摘要
仅仅由于外在和内在因素的存在,人类基因结构就经历了持续的磨损过程。在正常的生理细胞中,DNA 损伤会启动各种检查点,从而激活修复系统或诱导细胞凋亡,帮助维持细胞的完整性。而在癌细胞中,由于信号通路的改变和检查点的缺陷,存在着明显的无差错 DNA 修复/合成偏差。目前,以 DNA 损伤反应为靶点的癌症疗法具有显著的治疗潜力,可将非特异性疗法调整为肿瘤特异性疗法。最近,许多针对 DNA 复制酶的药物已经获得批准,或正在进行临床试验。PARP和PARG抑制剂等药物对癌细胞产生了巨大的作用。这篇综述重点介绍了针对 DNA 复制的不同药物类别的机理研究,从而描绘了靶向治疗的未来发展方向。
Mechanism-based Suppression of Cancer by Targeting DNA-Replicating Enzymes.
The human genetic structure undergoes continuous wear and tear process due to the mere presence of extrinsic as well as intrinsic factors. In normal physiological cells, DNA damage initiates various checkpoints that may activate the repair system or induce apoptosis that helps maintain cellular integrity. While in cancerous cells, due to alterations in signaling pathways and defective checkpoints, there exists a marked deviation of error-free DNA repairing/synthesis. Currently, cancer therapy targeting the DNA damage response shows significant therapeutic potential by tailoring the therapy from non-specific to tumor-specific activity. Recently, numerous drugs that target the DNA replicating enzymes have been approved or some are under clinical trial. Drugs like PARP and PARG inhibitors showed sweeping effects against cancer cells. This review highlights the mechanistic study of different drug categories that target DNA replication and thus depicts the futuristic approach of targeted therapy.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.