[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-338313-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-338313-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","chromatin-as-an-old-and-new-anti-cancer-target","Chromatin as an old and new anti-cancer target","","Recent genome-wide analyses identify chromatin modifiers as one of the most frequently mutated gene classes across all cancers, yet standard therapy still relies on DNA-damage-based chemotherapy for chromatin-deranged malignancies. The article proposes “chromatin damage” as nongenetic injury to protein-DNA interactions caused by certain small molecules. Anthracyclines are highlighted as an overlooked chromatin-targeting example, and emerging chromatin-damaging agents are discussed to support further studies and improve modern cancer treatment.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/chromatin-as-an-old-and-new-anti-cancer-target/338313/",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/chromatin-as-an-old-and-new-anti-cancer-target/338313.png","ImageObject",300,407,{"name":42,"@type":43},"River Wang","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What problem does the article address about current cancer chemotherapy?","Question",{"text":63,"@type":64},"Although chromatin modifiers are frequently mutated across cancers, therapies for chromatin-deranged tumors still mainly use DNA-damage-compromised chemotherapy as standard care.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What is “chromatin damage” as proposed in the paper?",{"text":68,"@type":64},"It refers to nongenetic damage to protein-DNA interactions induced by certain small molecules.",{"name":70,"@type":61,"acceptedAnswer":71},"Why are anthracyclines discussed as a key example?",{"text":72,"@type":64},"Anthracyclines are widely used chemotherapeutic agents and are presented as an overlooked chromatin-targeting class related to chromatin damage.","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},338313,1790151252,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,109,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",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":106,"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},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Trends Cancer. Author manuscript; available in PMC 2024 October 15. |\n| --- | --- |\n\nPublished in final edited form as:  \nTrends Cancer. 2024 August ; 10(8): 696–707. doi:10.1016/j.trecan.2024.05.005 .  \nChromatin as an old and new anti-cancer target  \nJacques Neefjes 1 , Katerina Gurova2,* , Jay Sarthy3 , Gábor Szabó4 , Steven Henikoff5  \n1–Department of Cell and Chemical Biology and Oncode Institute, LUMC, Einthovenweg 20, 2333 ZC Leiden, the Netherlands  \n2–Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA  \n3–Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Research Institute, 1920 Terry Ave, -Seattle, WA 98109, USA  \n4–Faculty of Medicine, Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, Egyetem tér 1, 4032 Hungary  \n5-Basic Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA  \nAbstract  \nRecent genome-wide analyses identified chromatin modifiers as one of the most frequently mutated class of genes across all cancers. However, chemotherapies developed for DNA damage-compromised cancers remain the standard of care for chromatin-deranged malignancies.  \nWe address this conundrum by establishing the concept of“chromatin damage”: the nongenetic damage to protein-DNA interactions induced by certain small molecules. We highlight anthracyclines, a class of chemotherapeutic agents ubiquitously applied in oncology, as an example of an overlooked chromatin-targeting agent. We discuss our current understanding of this phenomenon and explore emerging chromatin-damaging agents as a basis for further studies to maximize their impact in modern cancer treatment.  \nKeywords  \nchromatin damage; DNA damage; anthracyclines; cancer; curaxin  \nThis work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.  \n*[Correspondence: katerina.gurova@toswellpark.org](Correspondence: katerina.gurova@toswellpark.org).  \nDeclaration of interests  \nJN has shares in NIHM, a startup aiming to make aclarubicin available to the Western world. KG is a co-author of patents US9108916B2 “Carbazole compounds and therapeutic uses of the compounds”, US10434086B2 “Combination therapies with curaxins”, and US9169207B2 “Curaxins for use in treating carcinogen-induced cancer”.  \nThe authors do not have conflicts of interest, except that Jacques Neefjes is a shareholder of NIHM aimed at producing aclarubicin for clinical use.  \nPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.  \nAuthor Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \nNeefjes et al.  \nPage 2  \nA better look at DNA damage as chemotherapeutic activity  \nDespite recent developments in targeted therapies, conventional chemotherapy remains the standard of care for many cancers. One reason for the continued use of ‘old chemotherapy’in cancer is that drug resistance is more difficult to develop as most drugs target DNA.  \nWhile targeted therapy may be more specific, it can easily result in development of  \ndrug resistance through acquiring mutations or activation of parallel signaling pathways.  \n","cbCaidBtRvEP4FRI","https://ap.wps.com/l/cbCaidBtRvEP4FRI","pdf",1131921,23,"English","# Abstract\n# Keywords\n## A better look at DNA damage as chemotherapeutic activity\n## DNA as a dominant chemotherapy target\n## Side effects and toxicity of DNA-damaging drugs\n## Reconsidering DNA damage as a universal mechanism","[{\"question\":\"What problem does the article address about current cancer chemotherapy?\",\"answer\":\"Although chromatin modifiers are frequently mutated across cancers, therapies for chromatin-deranged tumors still mainly use DNA-damage-compromised chemotherapy as standard care.\"},{\"question\":\"What is “chromatin damage” as proposed in the paper?\",\"answer\":\"It refers to nongenetic damage to protein-DNA interactions induced by certain small molecules.\"},{\"question\":\"Why are anthracyclines discussed as a key example?\",\"answer\":\"Anthracyclines are widely used chemotherapeutic agents and are presented as an overlooked chromatin-targeting class related to chromatin damage.\"}]","Chromatin as an old and new anti-cancer target | PDF",1790023010,58]