[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-329110-105":3,"detail-sidebar-cat-0-en-105":73,"doc-detail-329110-en":122},{"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":66,"head_meta":68,"extra_data":70,"updated_unix":72},105,"en","targeting-mutant-p53-a-key-player-in-breast-cancer-pathogenesis-and-beyond","Targeting mutant p53 - a key player in breast cancer pathogenesis and beyond","","p53 mutation is the most common genetic alteration linked to human neoplasia, with TP53 missense mutations frequently arising early in breast cancer and present in over thirty percent of tumors. These mutations, especially in triple-negative breast cancer, drive more aggressive disease and poorer overall survival. Mutant p53s acquire gain-of-function while losing tumor-suppressive activity to varying degrees, creating tumor-specific dependencies and therapy resistance. By comparing cell/animal model data with clinical outcomes, the study clarifies mechanisms converting gene changes into mutant p53 tumorigenic effects, and reviews current and emerging p53-targeted treatments considering mutant–wild-type regulatory differences.",{"@graph":14,"@context":65},[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/targeting-mutant-p53-a-key-player-in-breast-cancer-pathogenesis-and-beyond/329110/",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/targeting-mutant-p53-a-key-player-in-breast-cancer-pathogenesis-and-beyond/329110.png","ImageObject",300,407,{"name":42,"@type":43},"Rowan","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",8,{"@type":57,"mainEntity":58},"FAQPage",[59],{"name":60,"@type":61,"acceptedAnswer":62},"How do mutant p53 mechanisms relate to therapy resistance?","Question",{"text":63,"@type":64},"The gain-of-function impact of stabilized mutant p53 creates tumor-specific dependency and contributes to resistance against therapy.","Answer","https://schema.org",{"og:url":32,"og:type":67,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":69,"canonical":32},"index,follow",{"doc_id":71,"site_id":7},329110,1790193836,{"code":4,"msg":74,"data":75},"success",[76,80,84,88,93,98,103,106,111,114,118],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":77,"show_sort_weight":78,"slug":79},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":81,"show_sort_weight":82,"slug":83},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Exam",70,"exam",{"id":89,"doc_module":4,"doc_module_name":25,"category_name":90,"show_sort_weight":91,"slug":92},5,"Comic",60,"comic",{"id":94,"doc_module":4,"doc_module_name":25,"category_name":95,"show_sort_weight":96,"slug":97},6,"Technology",50,"technology",{"id":99,"doc_module":4,"doc_module_name":25,"category_name":100,"show_sort_weight":101,"slug":102},7,"Healthcare",40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":104,"slug":105},30,"research-report",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},9,"Religion & Spirituality",20,"religion-spirituality",{"id":109,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":109,"slug":113},"World Cup","world-cup",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":115,"slug":117},10,"Lifestyle","lifestyle",{"id":119,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":89,"slug":121},19,"General","general",{"code":4,"msg":74,"data":123},{"doc_id":71,"user_id":124,"nickname":42,"user_avatar":125,"doc_module":4,"category_id":55,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":126,"file_id":127,"file_url":128,"file_type":129,"file_size":130,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":131,"language":132,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":133,"faqs":134,"seo_title":135,"seo_description":12,"update_tm":136,"read_time":137,"preview_page_count":4},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","Qayoom etal.  \nCell Communication and Signaling (2024) 22:484 [https://doi.org/10.1186/s12964-024-01863-9](https://doi.org/10.1186/s12964-024-01863-9)  \nCell Communication and Signaling  \n REVIEW Open Access  \nTargeting mutant p53: a key player in breast cancer pathogenesis and beyond  \nHina Qayoom1†, Burhan Ul Haq1†, Shazia Sofi1†, Nusrat Jan1, Asma Jan1 and Manzoor A. Mir 1*  \nAbstract  \nThe p53 mutation is the most common genetic mutation associated with human neoplasia. TP53 missense mutations, which frequently arise early in breast cancer, are present in over thirty percent of breast tumors. In breast cancer, p53 mutations are linked to a more aggressive course of the disease and worse overall survival rates. TP53 mutations are mostly seen in triple-negative breast cancer, a very diverse kind of the disease. The majority ofTP53 mutations originate in the replacement of individual amino acids within the p53 protein’s core domain, giving rise to a variety of variations referred to as \"mutant p53s.\" In addition to gaining carcinogenic qualities through gain-of-function pathways, these mutants lose the typical tumor-suppressive features of p53 to variable degrees. The gain-of-function impact of stabilized mutant p53 causes tumor-specific dependency and resistance to therapy. P53 is a prospective target for cancer therapy because of its tumor-suppressive qualities and the numerous alterations that it experiences in tumors. Phenotypic abnormalities in breast cancer, notably poorly differentiated basal-like tumors are frequently linked to high-grade tumors. By comparing data from cell and animal models with clinical outcomesin breast cancer, this study investigates the molecular mechanisms that convert gene alterations into the pathogenic consequences of mutant p53’s tumorigenic activity. The study delves into current and novel treatment approaches aimed at targeting p53 mutations, taking into account the similarities and differences in p53 regulatory mechanisms between mutant and wild-type forms, as well.  \nKeywords Breast cancer, Mutp53, Gain-of-function, HSP90, Ferroptosis, Metabolic reprogramming  \n†Hina Qayoom, Burhan Ul Haq and Shazia Sofi contributed equally to this work.  \n*Correspondence:  \nManzoor A. Mir  \n[drmanzoor@kashmiruniversity.ac.in](drmanzoor@kashmiruniversity.ac.in)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.)  \nQayoom etal. Cell Communication and Signaling (2024) 22:484 Page 2 of 14  \nGraphical Abstract  \nIntroduction  \nThe breast cancer is characterized by a high global incidence and besides affecting the breast tissue, it has the ability to metastasize to lungs and bones [1, 2]. The genome instability represents one of the cancer hallmarks [3, 4]. The frequently altered gene in cancers in humans is the tumor suppressor TP53, in almost 50% of all ","cbCaig4gFwyJNYC2","https://ap.wps.com/l/cbCaig4gFwyJNYC2","pdf",2240786,14,"English","# Abstract\n# Introduction\n## p53 regulation and TP53 mutations in cancer\n## p53 activation, MDM2 interaction, and downstream effects","[{\"question\":\"How do mutant p53 mechanisms relate to therapy resistance?\",\"answer\":\"The gain-of-function impact of stabilized mutant p53 creates tumor-specific dependency and contributes to resistance against therapy.\"}]","Targeting mutant p53 - a key player in breast cancer pathogenesis and beyond | PDF",1789982507,35]