摘要
基因组不稳定性(GI)是指基因组具有改变、增加的趋势,与肺癌的发生及治疗密切相关。在肺癌中,DNA损伤应答、错配修复、核苷酸切除修复、碱基切除修复及有丝分裂检查点等通路的异常,可促进核苷酸水平与染色体水平的不稳定性并驱动肿瘤生物学行为变化。针对这些机制的治疗手段也为肺癌治疗提供了有效途径。该文从核苷酸水平不稳定性、染色体不稳定性、表观遗传不稳定性、线粒体GI等方面系统性综述了GI在肺癌发生、发展中的作用与分子机制,重点叙述了核苷酸不稳定性与染色体不稳定性在肺癌发病中的研究进展,并总结了近期针对肺癌GI的相关临床研究及潜在治疗方法。尽管目前领域内取得了一些显著进展,但能够作为GI靶点治疗的基因仍然较为有限,未来随着基因测序及基因编辑技术的发展,会有更多针对GI基因的治疗靶点涌现,从而为肺癌的治疗提供新的策略和选择。
Genomic instability(GI)is defined as an increased or changed tendency of the genome and is closely associated with the development and treatment of lung cancer.In lung cancer,abnormalities in pathways such as DNA damage response,mismatch repair,nucleotide excision repair,base excision repair and the mitotic checkpoint promote instability at both the nucleotide and chromosomal levels,thereby driving changes in tumor biological behavior.Therapeutic strategies targeting these mechanisms provide effective approaches for the treatment of lung cancer.This article systematically reviews the roles and molecular mechanisms of GI in the initiation and progression of lung cancer from the perspectives of nucleotide-level instability,chromosomal instability,epigenetic instability,and mitochondrial GI.Particular emphasis is placed on recent advances in nucleotide and chromosomal instability related to lung cancer pathogenesis.Furthermore,recent clinical studies targeting GI in lung cancer and their potential therapeutic applications are summarized.Although notable progress has been made in this field,genes that can serve as therapeutic targets for GI remain limited.With the ongoing advancement of gene sequencing and gene-editing technologies,more GI-related therapeutic targets are expected to emerge,providing novel strategies and options for lung cancer treatment.
作者
闫娣
何审文
杨盈盈
高可琴
郑贵森
吴建军(综述)
马东京(审校)
YAN Di;HE Shenwen;YANG Yingying;GAO Keqin;ZHENG Guisen;WU Jianjun;MA Dongjing(School of Public Health,Gansu University of Chinese Medicine,Lanzhou,Gansu 730000,China)
出处
《检验医学与临床》
2025年第24期3440-3446,3452,共8页
Laboratory Medicine and Clinic
基金
国家自然科学基金项目(82160900)
甘肃省自然科学基金青年科技基金项目(23JRRA1726)
2022年度甘肃省高等学校创新基金项目(2022B-119)。
