[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-378336-105":59,"doc-detail-378336-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","targeting-epidermal-growth-factor-receptor-for-cancer-treatment-abolishing-both-kinase-dependent-and-kinase-independent-functions-of-the-receptor","Targeting Epidermal Growth Factor Receptor for Cancer Treatment - Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor","","Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase with oncogenic functions, is activated by ligand binding and drives cancer development through overexpression or mutation. Extensive EGFR-targeted therapies—including monoclonal antibodies, tyrosine kinase inhibitors, and a vaccine—have shown benefit only in limited cancer types, while intrinsic and acquired resistance remains common. Resistance mechanisms are complex and incompletely defined. This review analyzes both kinase-dependent and kinase-independent EGFR activities and their roles in therapeutic failure.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/targeting-epidermal-growth-factor-receptor-for-cancer-treatment-abolishing-both-kinase-dependent-and-kinase-independent-functions-of-the-receptor/378336/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/targeting-epidermal-growth-factor-receptor-for-cancer-treatment-abolishing-both-kinase-dependent-and-kinase-independent-functions-of-the-receptor/378336.png","ImageObject",300,407,{"name":92,"@type":93},"Grenda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are EGFR inhibitors effective only in some cancer types?","Question",{"text":112,"@type":113},"EGFR inhibitors target EGFR activation or tyrosine kinase activity, but clinical efficacy is limited to a few cancer types. Drug resistance, including intrinsic and acquired resistance, is common even where initial responses occur.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is the role of kinase-independent EGFR functions in resistance?",{"text":117,"@type":113},"The review highlights that EGFR can exert noncanonical oncogenic functions independent of its kinase activity. These kinase-independent functions may contribute crucially to cancer resistance to EGFR inhibitors.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the review organize kinase-dependent vs kinase-independent EGFR activity?",{"text":121,"@type":113},"It discusses kinase-dependent activities in sections covering activation, internalization/trafficking, and noncanonical locations. It then covers kinase-independent activities separately, followed by mechanisms and therapeutic activities of clinically used inhibitors.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},378336,1790534178,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},7971474921005,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","1521-0081/75/6/1218–1232$35 .00 [dx.doi.org/10.1124/pharmrev.123.000906](dx.doi.org/10.1124/pharmrev.123.000906)  \n[P](PHARMACOLOGICAL REVIEWS Pharmacol Rev 75:1218)[HARMACOLOGICAL](PHARMACOLOGICAL REVIEWS Pharmacol Rev 75:1218)[ R](PHARMACOLOGICAL REVIEWS Pharmacol Rev 75:1218)[EVIEWS](PHARMACOLOGICAL REVIEWS Pharmacol Rev 75:1218)[ Pharmacol Rev 75:1218](PHARMACOLOGICAL REVIEWS Pharmacol Rev 75:1218)–[1232](1232), [November 2023](November 2023)  \nCopyright © 2023 by The Author(s)  \nThis is an open access article distributed under the CC BY-NC Attribution 4 .0 International license.  \nASSOCIATE EDITOR: MICHAEL GOTTESMAN  \nTargeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor  \nYuesheng Zhang  \nDepartment of Pharmacology and Toxicology, School of Medicine, and Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, Virginia  \nAbstract ................................................................................. 1218  \nSignificance Statement ................................................................... 1219  \nI. Introduction ............................................................................. 1219  \nA. The Human Epidermal Growth Factor Receptor Family Receptor Tyrosine Kinases ..... 1219  \nB. Epidermal Growth Factor Receptor Overexpression and Mutation in Cancer ............ 1219  \nC. Clinically Used Epidermal Growth Factor Receptor Inhibitors ......................... 1220  \nD. Clinical Activities of Epidermal Growth Factor Receptor Inhibitors ..................... 1220  \nII. Kinase-Dependent Activities of Epidermal Growth Factor Receptor ......................... 1221  \nA. Ligand-Dependent and-Independent Activation of Epidermal Growth Factor Receptor Kinase 1221  \nB. Epidermal Growth Factor Receptor Internalization and Trafficking .................... 1222  \nC. Epidermal Growth Factor Receptor Functions in Noncanonical Locations ............... 1223  \nIII. Kinase-Independent Activities of Epidermal Growth Factor Receptor ....................... 1223  \nIV. Mechanisms of Actions And Therapeutic Activities of Clinically Used Epidermal Growth Factor Receptor Inhibitors ....................................................................... 1223  \nA. Tyrosine Kinase Inhibitors ........................................................... 1223  \nB. Monoclonal Antibodies ............................................................... 1224  \nC. CIMAvax ............................................................................ 1224  \nV. Sustained Epidermal Growth Factor Receptor Overexpression and Epidermal Growth Factor Receptor Crosstalk with Other Receptor Tyrosine Kinases to Counter Epidermal Growth Factor Receptor Inhibitors ....................................................................... 1225  \nA. Lack of Downregulation of Epidermal Growth Factor Receptor and Its Mutants Confers Resistance to Epidermal Growth Factor Receptor Inhibitors ........................... 1225  \nB. Heterodimerization of Epidermal Growth Factor Receptor and Its Mutants with Other Receptor Tyrosine Kinases Confers Resistance to Epidermal Growth Factor Receptor Inhibitors .... 1225  \nVI. Emerging Epidermal Growth Factor Receptor Degraders and Their Therapeutic Activities .. 1226  \nA. Proteolysis Targeting Chimeras ...................................................... 1226  \nB. Non-Proteolysis Targeting Chimera Small Molecules .................................. 1227  \nC. Antibody Combinations .............................................................. 1227  \nD. Non-Antibody Proteins ............................................................... 1228  \nVII. Concluding Remarks ..................................................................... 1228  \nAcknowledgments ........................................................................ 1228  \nReferences ...........................................................","cbCaiiXJhjTmRG6x","https://ap.wps.com/l/cbCaiiXJhjTmRG6x","pdf",1210621,15,"English","# Abstract\n# Significance Statement\n# Introduction\n## The Human Epidermal Growth Factor Receptor Family Receptor Tyrosine Kinases\n## Epidermal Growth Factor Receptor Overexpression and Mutation in Cancer\n## Clinically Used Epidermal Growth Factor Receptor Inhibitors\n## Clinical Activities of Epidermal Growth Factor Receptor Inhibitors\n# Kinase-Dependent Activities of Epidermal Growth Factor Receptor\n## Ligand-Dependent and Independent Activation of EGFR Kinase\n## EGFR Internalization and Trafficking\n## EGFR Functions in Noncanonical Locations\n# Kinase-Independent Activities of EGFR\n# Mechanisms of Actions and Therapeutic Activities of Clinically Used EGFR Inhibitors\n## Tyrosine Kinase Inhibitors\n## Monoclonal Antibodies\n## CIMAvax\n# Sustained EGFR Overexpression and Crosstalk with Other Receptor Tyrosine Kinases\n## Lack of Downregulation of EGFR and Its Mutants Confers Resistance\n## Heterodimerization with Other Receptor Tyrosine Kinases Confers Resistance\n# Emerging EGFR Degraders and Their Therapeutic Activities\n## Proteolysis Targeting Chimeras\n## Non-Proteolysis Targeting Chimera Small Molecules\n## Antibody Combinations\n## Non-Antibody Proteins\n# Concluding Remarks\n# Acknowledgments\n# References","[{\"question\":\"Why are EGFR inhibitors effective only in some cancer types?\",\"answer\":\"EGFR inhibitors target EGFR activation or tyrosine kinase activity, but clinical efficacy is limited to a few cancer types. Drug resistance, including intrinsic and acquired resistance, is common even where initial responses occur.\"},{\"question\":\"What is the role of kinase-independent EGFR functions in resistance?\",\"answer\":\"The review highlights that EGFR can exert noncanonical oncogenic functions independent of its kinase activity. These kinase-independent functions may contribute crucially to cancer resistance to EGFR inhibitors.\"},{\"question\":\"How does the review organize kinase-dependent vs kinase-independent EGFR activity?\",\"answer\":\"It discusses kinase-dependent activities in sections covering activation, internalization/trafficking, and noncanonical locations. It then covers kinase-independent activities separately, followed by mechanisms and therapeutic activities of clinically used inhibitors.\"}]","Targeting Epidermal Growth Factor Receptor for Cancer Treatment - Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor | PDF",1790229603,38]