DNA damage repair:historical perspectives,mechanistic pathways and clinical translation for targeted cancer therapy
作者机构：Department of Occupational and Environmental HealthXiangya School of Public HealthCentral South UniversityChangshaHunanChina Department of Radiation BiologyBeijing Key Laboratory for RadiobiologyBeijing Institute of Radiation MedicineAMMSBeijingChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第8期
页 面：2391-2425页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
基 金：This study was supported by grants from the National Natural Science Foundation of China(Grant No.82073486 U1803124 31870847 and 81842033)
摘 要：Genomic instability is the hallmark of various cancers with the increasing accumulation of DNA *** application of radiotherapy and chemotherapy in cancer treatment is typically based on this property of ***,the adverse effects including normal tissues injury are also accompanied by the radiotherapy and *** cancer therapy has the potential to suppress cancer cells DNA damage response through tailoring therapy to cancer patients lacking specific DNA damage response ***,understanding the broader role of DNA damage repair in cancers has became a basic and attractive strategy for targeted cancer therapy,in particular,raising novel hypothesis or theory in this field on the basis of previous scientists findings would be important for future promising druggable emerging *** this review,we first illustrate the timeline steps for the understanding the roles of DNA damage repair in the promotion of cancer and cancer therapy developed,then we summarize the mechanisms regarding DNA damage repair associated with targeted cancer therapy,highlighting the specific proteins behind targeting DNA damage repair that initiate functioning abnormally duo to extrinsic harm by environmental DNA damage factors,also,the DNA damage baseline drift leads to the harmful intrinsic targeted cancer *** addition,clinical therapeutic drugs for DNA damage and repair including therapeutic effects,as well as the strategy and scheme of relative clinical trials were intensive *** on this background,we suggest two hypotheses,namelyenvironmental gear selectionto describe DNA damage repair pathway evolution,andDNA damage baseline drift,which may play a magnified role in mediating repair during cancer *** two new hypothesis would shed new light on targeted cancer therapy,provide a much better or more comprehensive holistic view and also promote the development of new research direction and new overcoming strategies for
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