DNA damage repair:historical perspectives,mechanistic pathways and clinical translation for targeted cancer therapy

查看全文 作　　者：Ruixue [1]Huang;Ping-Kun [2]Zhou

机构地区：[1]Department of Occupational and Environmental Health,Xiangya School of Public Health,Central South University,Changsha,Hunan,China;[2]Department of Radiation Biology,Beijing Key Laboratory for Radiobiology,Beijing Institute of Radiation Medicine,AMMS,Beijing,China

出　　处：《Signal Transduction and Targeted Therapy》索引2021年第6卷第8期,共35页

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 damage.The application of radiotherapy and chemotherapy in cancer treatment is typically based on this property of cancers.However,the adverse effects including normal tissues injury are also accompanied by the radiotherapy and chemotherapy.Targeted cancer therapy has the potential to suppress cancer cells'DNA damage response through tailoring therapy to cancer patients lacking specific DNA damage response functions.Obviously,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 targets.In 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 therapy.In 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 discussed.Based on this background,we suggest two hypotheses,namely'environmental gear selection”to describe DNA damage repair pathway evolution,and'DNA damage baseline drift”,which may play a magnified role in mediating repair during cancer treatment.This 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 patients. 关键词：DAMAGE CLINICAL TARGETED

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DNA damage repair:historical perspectives,mechanistic pathways and clinical translation for targeted cancer therapy

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