[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-382616-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-382616-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","the-expanding-role-of-iap-antagonists-for-the-treatment-of-head-and-neck-cancer","The expanding role of IAP antagonists for the treatment of head and neck cancer","","Inhibitors of apoptosis proteins (IAPs) block intrinsic and extrinsic cell death pathways, supporting cancer cell survival. Many head and neck squamous cell carcinomas (HNSCCs) carry genomic alterations in IAP-related pathways, creating vulnerability to IAP antagonist therapy. Preclinical findings suggest IAP antagonists, including SMAC mimetics, may work particularly with radiation, supported by both pro-death and immune mechanisms such as immunogenic cell death and T-cell activation. Early phase I/II trials show promising clinical signals.",{"@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/the-expanding-role-of-iap-antagonists-for-the-treatment-of-head-and-neck-cancer/382616/",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/the-expanding-role-of-iap-antagonists-for-the-treatment-of-head-and-neck-cancer/382616.png","ImageObject",300,407,{"name":42,"@type":43},"Aria Callaghan","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What are IAPs and why are they important in head and neck cancer?","Question",{"text":63,"@type":64},"IAPs inhibit apoptosis and are often overexpressed in cancer cells, contributing to resistance to chemotherapy and radiation. Alterations in IAP pathways in HNSCC can make tumors susceptible to IAP antagonists.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do IAP antagonists act in cancer models?",{"text":68,"@type":64},"IAP antagonists target IAP proteins, promote degradation of IAPs, and thereby enable caspase activation and apoptotic cascades. They can also support immune mechanisms such as immunogenic cell death and T-cell activation.",{"name":70,"@type":61,"acceptedAnswer":71},"Why is combination with radiation highlighted?",{"text":72,"@type":64},"Radiation therapy activates IAP pathways, so IAP antagonists can function as radiosensitizers. The review emphasizes improved efficacy when IAP antagonists are combined with radiation therapy.","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},382616,1790794490,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"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":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":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"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":107,"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":111,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":117},962084926284,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","DOI: 10. 1002/cam4 .6011  \nREVIEW  \nThe expanding role ofIAP antagonists for the treatment of head and neck cancer  \nVikash Kansal1,2  | Brendan L. C. Kinney1,2 | Srijayaprakash Uppada2,3 | Nabil F. Saba2,4 | William A. Stokes2,3 | Zachary S. Buchwald2,3 | Nicole C. Schmitt1,2   \n1Department of Otolaryngology – Head and Neck Surgery, Emory University, Atlanta, Georgia, USA  \n2Winship Cancer Institute, Emory University, Atlanta, Georgia, USA 3Department of Radiation Oncology, Emory University, Atlanta, Georgia, USA  \n4Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia, USA  \nCorrespondence  \nNicole C. Schmitt, Department of Otolaryngology – Head and Neck Surgery, Translational Research, Head and Neck Cancer Program, Winship Cancer Institute, Emory University School of Medicine, 550 Peachtree Street NE, 11th Floor Otolaryngology, Atlanta, GA 30308, USA.  \nEmail: nicole.cherie.schmitt@emory. edu  \n1 | INTRODUCTION  \nAbstract  \nInhibitors of apoptosis proteins (IAPs) inhibit the intrinsic and extrinsic cell death pathways, promoting cell survival. Antagonists of these pathways are under study as anti-cancer therapeutics. A high proportion of head and neck squamous cell carcinomas (HNSCCs) have genomic alterations in IAP pathways, resulting in the dysregulation of cell death pathways and rendering them susceptible to IAP antagonist therapy. Preclinical studies suggest IAP antagonists, also known as second mitochondria-derived activator of caspases mimetics, may be effective treatments for HNSCC, especially when combined with radiation. Mechanistic studies have shown both molecular mechanisms (i.e., enhanced cell death) and immune mechanisms (e.g., immunogenic cell death and T-cell activation), underlying the efficacy of these drugs in preclinical models. Phase I/II clinical trials have shown promising results, portending a future where this class of targeted therapies becomes incorporated into the treatment paradigm for head and neck cancers. IAP antagonists have shown great promise for head and neck cancer, especially in combination with radiation therapy. Here, we review recent preclinical and clinical studies on the use of these novel targeted agents for head and neck cancer.  \nKEYWORDS  \nbirinapant, head and neck cancer, IAP antagonist, SMAC mimetic, squamous cell carcinoma, tolinapant, xevinapant  \nHead and neck squamous cell carcinoma (HNSCC) encompasses two distinct disease processes: oropharyn-  \nDrugs antagonizing specific signaling pathways to induce cell death are under rigorous study for a variety of treatment-refractory solid tumors. In cases where the signaling pathways in question are rare, targeted therapies offer an opportunity for precision medicine. However, the ideal targeted therapies will be effective for most patients with a given cancer, obviating the need for pretreatment molecular screening.  \ngeal carcinoma driven by high-risk human papillomavirus (HPV) and HPV-negative HNSCC, which is typically linked to heavy use of tobacco and/or alcohol. Cetuximab, a chimeric mouse/human anti-EGFR antibody, was the first FDA-approved targeted agent for HNSCC. However, despite EGFR overexpression in 90% of head and neck cancers, cetuximab has shown inferior efficacy compared with standard cisplatin chemotherapy for HNSCC.1 As a  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.  \nKANSAL et al.  \n|  \n13959  \nresult, there is still an unmet need for effective targeted therapies to treat HNSCC.  \nSmall-molecule drugs inhibiting the inhibitor of apoptosis proteins (IAPs) have shown promising activity in both HPV-driven and HPV-negative HNSCC, both in preclinical models and early clinical studies. IAP pathways are activated by radiation therapy (RT); thus IAP antagonists","cbCaijRVpmZ9JYgx","https://ap.wps.com/l/cbCaijRVpmZ9JYgx","pdf",453996,"English","# Introduction\n## Inhibitor of apoptosis proteins and related pathways","[{\"question\":\"What are IAPs and why are they important in head and neck cancer?\",\"answer\":\"IAPs inhibit apoptosis and are often overexpressed in cancer cells, contributing to resistance to chemotherapy and radiation. Alterations in IAP pathways in HNSCC can make tumors susceptible to IAP antagonists.\"},{\"question\":\"How do IAP antagonists act in cancer models?\",\"answer\":\"IAP antagonists target IAP proteins, promote degradation of IAPs, and thereby enable caspase activation and apoptotic cascades. They can also support immune mechanisms such as immunogenic cell death and T-cell activation.\"},{\"question\":\"Why is combination with radiation highlighted?\",\"answer\":\"Radiation therapy activates IAP pathways, so IAP antagonists can function as radiosensitizers. The review emphasizes improved efficacy when IAP antagonists are combined with radiation therapy.\"}]","The expanding role of IAP antagonists for the treatment of head and neck cancer | PDF",1790251357]