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Autophagy, a self-degradation and recycling pathway, is highlighted as a therapeutic target, with dysregulation linked to cancer progression and drug resistance. The review emphasizes the relationship among autophagy, DNA damage, and DNA repair homeostasis, with particular attention to BRCA1/2 mutations and therapy implications.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/complex-interplay-between-dna-damage-and-autophagy-in-disease-and-therapy-review/331211/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/complex-interplay-between-dna-damage-and-autophagy-in-disease-and-therapy-review/331211.png","ImageObject",300,407,{"name":42,"@type":43},"Asher","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-15","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How does genomic and molecular aberration contribute to cancer complexity?","Question",{"text":63,"@type":64},"Genomic and molecular aberrations, combined with environmental factors, contribute to cancer heterogeneity and complexity by driving diverse molecular behaviors within tumors.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why is doxorubicin effective yet clinically limited?",{"text":68,"@type":64},"Doxorubicin shows efficacy against various cancers, but its use is constrained by dose-dependent cytotoxicity that can harm vital organs, including the heart and brain.",{"name":70,"@type":61,"acceptedAnswer":71},"What role does autophagy play in cancer and therapy outcomes?",{"text":72,"@type":64},"Autophagy is involved in self-degradation and recycling; dysregulation contributes to cancer progression and drug resistance, while modulating autophagy may improve treatment outcomes and reduce adverse effects.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},331211,1791062524,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","biomolecules  \nReview  \nComplex Interplay between DNA Damage and Autophagy in Disease and Therapy  \nAman Singh 1, Naresh Ravendranathan 1, Jefferson C. Frisbee 1 and Krishna K. Singh 1,2, *  \nCitation: Singh, A.; Ravendranathan, N.; Frisbee, J.C.; Singh, K.K. Complex Interplay between DNA Damage and Autophagy in Disease and Therapy. Biomolecules 2024, 14, 922. [https://](https://)[ ](https://)[doi.org/10.3390/biom14080922](doi.org/10.3390/biom14080922)  \nAcademic Editors: Da-Tian Bau and Shunbin Ning  \nReceived: 25 June 2024  \nRevised: 19 July 2024  \nAccepted: 26 July 2024  \nPublished: 29 July 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond Street North, London, ON N6A 5C1, Canada; [asing945@uwo.ca](asing945@uwo.ca) (A.S.);  \n[nravendr@uwo.ca](nravendr@uwo.ca) (N.R.); [jfrisbee@uwo.ca](jfrisbee@uwo.ca) (J.C.F.)  \n2 Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada  \n* Correspondence: [krishna.singh@uwo.ca](krishna.singh@uwo.ca); Tel.: +1-(519)-661-2111 (ext. 80542 or 85683)  \nAbstract: Cancer, a multifactorial disease characterized by uncontrolled cellular proliferation, remains a global health challenge with significant morbidity and mortality. Genomic and molecular aberrations, coupled with environmental factors, contribute to its heterogeneity and complexity. Chemotherapeutic agents like doxorubicin (Dox) have shown efficacy against various cancers but are hindered by dose-dependent cytotoxicity, particularly on vital organs like the heart and brain. Autophagy, a cellular process involved in self-degradation and recycling, emerges as a promising therapeutic target in cancer therapy and neurodegenerative diseases. Dysregulation of autophagy contributes to cancer progression and drug resistance, while its modulation holds the potential to enhance treatment outcomes and mitigate adverse effects. Additionally, emerging evidence suggests a potential link between autophagy, DNA damage, and caretaker breast cancer genes BRCA1/2, highlighting the interplay between DNA repair mechanisms and cellular homeostasis. This review explores the intricate relationship between cancer, Dox-induced cytotoxicity, autophagy modulation, and the potential implications of autophagy in DNA damage repair pathways, particularly in the context of BRCA1/2 mutations.  \nKeywords: autophagy; cancer; doxorubicin; BRCA1/2; DNA damage  \n1. Introduction  \nCancer, a complex and heterogeneous disease, remains a significant global health challenge characterized by uncontrolled cellular proliferation and growth due to genomic and molecular aberrations [1] . Cancer cells evade immune surveillance and exploit neighboring cells’ physiology to sustain their proliferation [2] . The metabolic mechanisms of cancer cells significantly overlap with those of host cells, posing a formidable challenge to cancer treatment [3] . In 2022 alone, the World Health Organization (WHO) reported a staggering 20 million new cancer cases worldwide, accompanied by 9.7 million cancer-related deaths, with projections indicating a rise to 35 million cases by 2050 [4] . Among the myriad cancer types, breast cancer ranks as the most prevalent [4] . These cancers arise from a combination of internal factors, such as inherited mutations and external factors acquired from the environment and infectious organisms [5](Figure 1) . Notably, DNA damage emerges as a critical player in cancer development, stemming mainly from mutations due to exposure to radiation or genotoxic agents or errors ","cbCaiu5VoGSQL7QM","https://ap.wps.com/l/cbCaiu5VoGSQL7QM","pdf",4165702,27,"English","# Introduction\n## Cancer heterogeneity and genomic aberrations\n## DNA damage as a driver of cancer development\n## DNA damage sources and lesion types\n## DNA repair pathways\n# Abstract and scope of the review\n## Autophagy as a therapeutic target\n## Doxorubicin toxicity and treatment challenges\n## Links among autophagy, DNA damage, and BRCA1/2","[{\"question\":\"How does genomic and molecular aberration contribute to cancer complexity?\",\"answer\":\"Genomic and molecular aberrations, combined with environmental factors, contribute to cancer heterogeneity and complexity by driving diverse molecular behaviors within tumors.\"},{\"question\":\"Why is doxorubicin effective yet clinically limited?\",\"answer\":\"Doxorubicin shows efficacy against various cancers, but its use is constrained by dose-dependent cytotoxicity that can harm vital organs, including the heart and brain.\"},{\"question\":\"What role does autophagy play in cancer and therapy outcomes?\",\"answer\":\"Autophagy is involved in self-degradation and recycling; dysregulation contributes to cancer progression and drug resistance, while modulating autophagy may improve treatment outcomes and reduce adverse effects.\"}]","Complex Interplay between DNA Damage and Autophagy in Disease and Therapy - Review | PDF",1789992226,68]