[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-56182-en":3,"doc-seo-56182-105":29,"detail-sidebar-cat-0-en-105":90},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":4,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":13,"seo_description":14,"update_tm":27,"read_time":28},56182,4810365810221,"Aurora","https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d",8,"Research & Report","DNA damage response and neoantigens: a favorable target for triple-negative breast cancer immunotherapy and vaccine development","Triple-negative breast cancer (TNBC) presents clinical difficulty due to aggressive behavior and restricted options, motivating targeted immunotherapy and vaccine strategies. DNA damage response (DDR) forms a regulatory network that preserves genomic integrity, yet TNBC’s genomic instability drives dysregulated DDR and increases tumor mutation burden. Somatic mutations generate neoantigens that can be presented on MHC molecules, enabling immune recognition. The review links DDR-related neoantigen immunogenicity to cancer-vaccine and immunotherapy modalities, including immune checkpoint inhibitors, adoptive cell therapy, and personalized vaccine design for precision medicine.","CHAPTERTHREE  \n# DNA damage response andneoantigens:A favorabletarget for triple-negative\n\nbreast cancer immunotherapyand vaccine development  \nRajasekaran Subbarayana,1,Dhasarathdev Srinivasana,1,RanjithBalakrishnana,1,Ajeet Kumarb,1,Salman Sadullah UsmaniC*andNityanand Srivastavad*,aCentre for Advanced Biotherapeutics andRegenerative Medicine,FAHS,Chettinad Hospital and ResearchInstitute,Chettinad Academy of Research and Education,Kelambakkam,India,  Department of Psychiatry,Washingtonuniversity School of Medicine,St louis,MO,United  \nStates,  Department of Molecular Pharmacology,Albert EinsteinCollege of Medicine,Bronx,NY,United States,dDepartment of CellBiology,Albert Einstein College of Medicine,Bronx,NY,UnitedStates,*Corresponding authors.salman.usmani@einsteinmed.edu;nityanand.srivastava@einsteinmed.edu  \n## Abstract\n\nTriple-negative breast cancer(TNBC)poses a significant clinicalchallenge due to its aggressive nature and limited therapeuticoptions.The interplay between DNA damage response(DDR)mechanisms and the emergence of neoantigens represents apromising avenue for developing targeted immunotherapeuticstrategies and vaccines for TNBC.The DDR is a complex networkof cellular mechanisms designed to maintain genomic integrity.InTNBC,where genetic instability is a hallmark,dysregulation ofDDR components plays a pivotal role in tumorigenesis andprogression.This review explores the intricate relationshipbetween DDR and neoantigens,shedding light on the potentialvulnerabilities of TNBC cells.Neoantigens,arising from somaticmutations in cancer cells,represent unique antigens that can berecognized by the immune system.TNBC's propensity forgenomic instability leads to an increased mutational burden,consequently yielding a rich repertoire of neoantigens.Theconvergence of DDR and neoantigens in TNBC offers a distinctiveopportunity for immunotherapeutic targeting.Immunotherapyhas revolutionized cancer treatment by harnessing the immunesystem to selectively target cancer cells.The unique  \nimmunogenicity conferred by DDR-related neoantigens in TNBCpositions them as ideal targets for immunotherapeuticinterventions.This review also explores various  \nimmunotherapeutic modalities,including immune checkpointinhibitors(ICIs),adoptive cell therapies,and cancer vaccines,thatleverage the DDR and neoantigen interplay to enhance anti-tumorimmune responses.Moreover,the potential for developingvaccines targeting DDR-related neoantigens opens new frontiers  \nin preventive and therapeutic strategies for TNBC.The rationaldesign of vaccines tailored to the individual mutational landscapeof TNBC holds promise for precision medicine approaches.Inconclusion,the convergence of DDR and neoantigens in TNBCpresents a compelling rationale for the development of innovativeimmunotherapies and vaccines.Understanding and targetingthese interconnected processes may pave the way for personalizedand effective interventions,offering new hope for patientsgrappling with the challenges posed by TNBCs.  \nKeywords  \nTNBC;Immunotherapy;Neoantigen;DNA damage response;Vaccine  \n## 1Introduction\n\nDDR pathways play a pivotal role in safeguarding cells againstacquired genomic alterations,monitoring DNA damage,andpreserving genomic integrity through DNA repair mechanisms(Giglia-Mari,Zotter,&Vermeulen,2011;Huang &Zhou,2021;Jiang et al.,2021;Zhou &Elledge,2000).However,in thecontext of cancer,DDR presents a dual-faced aspect.Alterations inDDR genes can instigate genomic mutations,thereby promotinggenomic instability,a hallmark of many cancer types.Conversely,theaccumulation of mutations induced by DNA damage,known as tumormutation burden(TMB),can generate neoantigens-abnormalproteins do not present in healthy tissue.These neoantigens,presented on cancer cell surfaces via Major HistocompatibilityComplex(MHC),evoke an immune response(Giglia-Mari et al.,2011;Schumacher,Scheper,&Kvistborg,2019;Sha et al.,  \n2020;Wang et al.,2023).Analysis of databases like The CancerGenome Atlas(","cbCainjbGoP6jnPD","https://ap.wps.com/l/cbCainjbGoP6jnPD","pdf",6649928,1,87,"English","en",105,"# Abstract\n# 1 Introduction\n# 2 DDR signaling","[{\"question\":\"How does the DNA damage response (DDR) relate to neoantigen formation in TNBC?\",\"answer\":\"DDR supports genomic integrity, but in TNBC dysregulation contributes to genomic instability. Increased mutations raise the tumor mutation burden, which in turn generates somatic neoantigens that can be recognized by the immune system.\"},{\"question\":\"Why are neoantigens considered favorable targets for TNBC immunotherapy?\",\"answer\":\"DDR-driven genomic instability increases mutational burden, producing a richer repertoire of neoantigens. When presented on MHC by cancer cells, DDR-related neoantigens can elicit anti-tumor immune responses, supporting targeted immunotherapeutic strategies.\"},{\"question\":\"Which immunotherapeutic modalities does the review connect to the DDR–neoantigen interplay?\",\"answer\":\"The review discusses immune checkpoint inhibitors (ICIs), adoptive cell therapies, and cancer vaccines. These approaches aim to enhance anti-tumor immune responses by leveraging DDR-associated neoantigen immunogenicity.\"}]",1783718258,219,{"code":4,"msg":30,"data":31},"ok",{"site_id":24,"language":23,"slug":32,"title":13,"keywords":33,"description":14,"schema_data":34,"social_meta":85,"head_meta":87,"extra_data":89,"updated_unix":27},"dna-damage-response-and-neoantigens-a-favorable-target-for-triple-negative-breast-cancer-immunotherapy-and-vaccine-development","",{"@graph":35,"@context":84},[36,53,67],{"@type":37,"itemListElement":38},"BreadcrumbList",[39,43,47,50],{"item":40,"name":41,"@type":42,"position":20},"https://docshare.wps.com","Home","ListItem",{"item":44,"name":45,"@type":42,"position":46},"https://docshare.wps.com/document/","Document",2,{"item":48,"name":12,"@type":42,"position":49},"https://docshare.wps.com/document/research-report/",3,{"item":51,"name":13,"@type":42,"position":52},"https://docshare.wps.com/document/dna-damage-response-and-neoantigens-a-favorable-target-for-triple-negative-breast-cancer-immunotherapy-and-vaccine-development/56182/",4,{"url":51,"name":13,"@type":54,"author":55,"headline":13,"publisher":57,"fileFormat":60,"inLanguage":23,"description":14,"dateModified":61,"datePublished":61,"encodingFormat":60,"isAccessibleForFree":62,"interactionStatistic":63},"DigitalDocument",{"name":9,"@type":56},"Person",{"url":40,"name":58,"@type":59},"DocShare","Organization","application/pdf","2026-07-10",true,{"@type":64,"interactionType":65,"userInteractionCount":4},"InteractionCounter",{"@type":66},"ViewAction",{"@type":68,"mainEntity":69},"FAQPage",[70,76,80],{"name":71,"@type":72,"acceptedAnswer":73},"How does the DNA damage response (DDR) relate to neoantigen formation in TNBC?","Question",{"text":74,"@type":75},"DDR supports genomic integrity, but in TNBC dysregulation contributes to genomic instability. Increased mutations raise the tumor mutation burden, which in turn generates somatic neoantigens that can be recognized by the immune system.","Answer",{"name":77,"@type":72,"acceptedAnswer":78},"Why are neoantigens considered favorable targets for TNBC immunotherapy?",{"text":79,"@type":75},"DDR-driven genomic instability increases mutational burden, producing a richer repertoire of neoantigens. When presented on MHC by cancer cells, DDR-related neoantigens can elicit anti-tumor immune responses, supporting targeted immunotherapeutic strategies.",{"name":81,"@type":72,"acceptedAnswer":82},"Which immunotherapeutic modalities does the review connect to the DDR–neoantigen interplay?",{"text":83,"@type":75},"The review discusses immune checkpoint inhibitors (ICIs), adoptive cell therapies, and cancer vaccines. These approaches aim to enhance anti-tumor immune responses by leveraging DDR-associated neoantigen immunogenicity.","https://schema.org",{"og:url":51,"og:type":86,"og:title":13,"og:site_name":58,"og:description":14},"article",{"robots":88,"canonical":51},"index,follow",{"doc_id":7,"site_id":24},{"code":4,"msg":5,"data":91},[92,96,100,104,109,114,119,122,127,130,134],{"id":20,"doc_module":4,"doc_module_name":45,"category_name":93,"show_sort_weight":94,"slug":95},"Story & Novel",90,"story-novel",{"id":46,"doc_module":4,"doc_module_name":45,"category_name":97,"show_sort_weight":98,"slug":99},"Literature",80,"literature",{"id":52,"doc_module":4,"doc_module_name":45,"category_name":101,"show_sort_weight":102,"slug":103},"Exam",70,"exam",{"id":105,"doc_module":4,"doc_module_name":45,"category_name":106,"show_sort_weight":107,"slug":108},5,"Comic",60,"comic",{"id":110,"doc_module":4,"doc_module_name":45,"category_name":111,"show_sort_weight":112,"slug":113},6,"Technology",50,"technology",{"id":115,"doc_module":4,"doc_module_name":45,"category_name":116,"show_sort_weight":117,"slug":118},7,"Healthcare",40,"healthcare",{"id":11,"doc_module":4,"doc_module_name":45,"category_name":12,"show_sort_weight":120,"slug":121},30,"research-report",{"id":123,"doc_module":4,"doc_module_name":45,"category_name":124,"show_sort_weight":125,"slug":126},9,"Religion & Spirituality",20,"religion-spirituality",{"id":125,"doc_module":4,"doc_module_name":45,"category_name":128,"show_sort_weight":125,"slug":129},"World Cup","world-cup",{"id":131,"doc_module":4,"doc_module_name":45,"category_name":132,"show_sort_weight":131,"slug":133},10,"Lifestyle","lifestyle",{"id":135,"doc_module":4,"doc_module_name":45,"category_name":136,"show_sort_weight":105,"slug":137},19,"General","general"]