[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-356589-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-356589-en":131},{"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","p53-from-understanding-therapeutic-targeting-review-article-open","p53: from understanding therapeutic targeting - Review Article Open","","p53 is the most frequently mutated tumor suppressor gene in human cancers, where the encoded p53 protein regulates apoptosis, autophagy, cell cycle arrest, metabolism, senescence, and the tumor immune microenvironment to restrain tumorigenesis. TP53 mutations can abolish tumor suppression and create carcinogenic properties, yet p53-targeting drugs remain largely in early clinical development and are still considered “undruggable.” Recent advances include MDM2/4 antagonists, mutant-specific targeting, restoration of wild-type p53 function, p53-based genetic therapies, and p53-based tumor immunotherapy.",{"@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/p53-from-understanding-therapeutic-targeting-review-article-open/356589/",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/p53-from-understanding-therapeutic-targeting-review-article-open/356589.png","ImageObject",300,407,{"name":42,"@type":43},"Kyle","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",13,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is p53 considered a key target in oncology?","Question",{"text":63,"@type":64},"p53 is frequently mutated in human cancers and controls multiple anti-tumor processes including apoptosis, autophagy, cell cycle arrest, metabolism, and senescence, as well as shaping the tumor immune microenvironment.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What does the document say about targeting p53 drugs and approval status?",{"text":68,"@type":64},"Drugs targeting p53 are still under investigation in early clinical trials and have not been approved for clinical use, consistent with the view that p53 is widely regarded as “undruggable.”",{"name":70,"@type":61,"acceptedAnswer":71},"What newer therapeutic strategies targeting p53 are highlighted?",{"text":72,"@type":64},"The review discusses approaches such as MDM2/4 antagonists, compounds targeting specific p53 mutants or restoring wild-type function, p53-based genetic therapies, and p53-based tumor immunotherapy.","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},356589,1790176429,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},3985741905716,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Signal Transduction [and Targeted Therapy](and Targeted Therapy www.nature.com/sigtrans)[ www.nature.com/sigtrans](and Targeted Therapy www.nature.com/sigtrans)  \nREVIEW ARTICLE OPEN  \np53: from understanding therapeutic targeting  \nits structure to advances in  \nWenhua Wang 1, Xia Liu1, Hengqi Liu1, Hassan Abolhassani2, Han Yan3, Huilai Zhang 1 ✉ and Xianhuo Wang 1 ✉  \n\n|  | The tumor suppressor gene TP53 is the most frequently mutated gene in human cancers and has been a popular area of research in the field of oncology. The p53 protein, encoded by the TP53 gene, not only binds to many targeted genes but also regulates apoptosis, autophagy, cell cycle arrest, metabolism, senescence and the tumor immune microenvironment to suppress tumorigenesis. In recent years, an increasing number of new functions of p53 have been discovered, and p53-mediated tumor suppressor functions have been greatly expanded. Mutations in TP53 not only abolish its ability to suppress tumorigenesis but also confer carcinogenic properties to p53-mutant cells. Because of the prevalence of p53 dysfunction in various disease types, p53 has long been considered an attractive target for new anticancer drugs. However, drugs targeting p53 are still under investigation in early clinical trials and have not been approved for clinical use. This finding is consistent with the speculation that p53 is widely regarded as “undruggable.” Surprisingly, several novel therapeutic approaches targeting p53, including MDM2/4 antagonists, compounds that target specific p53 mutants or restore the wild-type function of the mutated p53 protein, p53-based genetic therapies and p53-based tumor immunotherapy, have been developed in recent years. Here, we present a review of the structure, inactivation, and roles of p53 in diseases. In addition, this review discusses the efforts to target diseases associated with p53 |  |  |  |\n| --- | --- | --- | --- | --- |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n| dysfunction and the challenges encountered in the |  | clinical | development of these approaches. |  |\n|  | Signal Transduction and Targeted Therapy (2026)11:1 | 21 | ; [https://doi.org/10.1038/s41392-025-02549-5](https://doi.org/10.1038/s41392-025-02549-5) |  |\n|  |  |  |  |  |\n\nINTRODUCTION  \nThe p53 protein, encoded by the TP53 gene, is expressed in almost all human tissues and plays a pivotal role in cancer suppression as a tumor suppressor. The transcription factor activity of p53 modulates the expression of specific genes involved in the following processes: apoptosis, cell cycle arrest, metabolism, senescence, ferroptosis, and autophagy.1,2 Generally, TP53 is regarded as the “guardian of the genome” and is widely considered one of the most critical genes that protects humans from tumorigenesis.3 However, mutations in TP53 occur in most human cancers,4 which can abrogate the anticancer activity of TP53 and confer cancerogenic properties to mutant p53 proteins.5 Mutations in TP53 are thought to occur in more than 50% of all human malignancies.6,7 The TP53 mutation rate exceeds 70% in certain subtypes of cancers, including squamous esophageal cancer, small-cell lung cancer, squamous cell lung cancer, and complex karyotype acute myeloid leukemia (AML), and is lower in partial tumors such as lymphoma, melanoma, and overall AML.8–11  \nBecause of its tumor suppressor function and universal mutation in human cancer, p53 is a highly appealing target for new anticancer therapies. Therapeutic strategies targeting TP53 mutations require reactivation of proteins. Nevertheless, major small-molecule drugs used for cancer therapy act by suppressing protein activity. Therefore, p53 is widely regarded  \nas “undruggable”.12 Although a series of therapeutic approaches targeting p53 mutations began developing decades ago, little progress has been made. A small","cbCairoDVhwKS7Zq","https://ap.wps.com/l/cbCairoDVhwKS7Zq","pdf",3237123,38,"English","# Introduction\n## Targeting p53 in cancer therapy\n## Therapeutic approaches and current limitations","[{\"question\":\"Why is p53 considered a key target in oncology?\",\"answer\":\"p53 is frequently mutated in human cancers and controls multiple anti-tumor processes including apoptosis, autophagy, cell cycle arrest, metabolism, and senescence, as well as shaping the tumor immune microenvironment.\"},{\"question\":\"What does the document say about targeting p53 drugs and approval status?\",\"answer\":\"Drugs targeting p53 are still under investigation in early clinical trials and have not been approved for clinical use, consistent with the view that p53 is widely regarded as “undruggable.”\"},{\"question\":\"What newer therapeutic strategies targeting p53 are highlighted?\",\"answer\":\"The review discusses approaches such as MDM2/4 antagonists, compounds targeting specific p53 mutants or restoring wild-type function, p53-based genetic therapies, and p53-based tumor immunotherapy.\"}]","p53: from understanding therapeutic targeting - Review Article Open | PDF",1790126082,96]