[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-361722-105":59,"doc-detail-361722-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","sunvozertinib-shining-light-on-lung-cancers-exon-20-fight","Sunvozertinib: shining light on lung cancer’s exon 20 fight","","Sunvozertinib is discussed as a targeted therapeutic focus for non-small cell lung cancer (NSCLC) driven by EGFR exon 20 insertion mutations (Ex20ins). The commentary explains why Ex20ins are clinically important yet difficult to detect, noting that PCR-based assays can miss a substantial fraction and that comprehensive genomic testing is often necessary. It reviews known molecular mechanisms behind reduced response to first-generation EGFR TKIs, describes heterogeneity by insertion site, and summarizes emerging sensitivity patterns to later-generation inhibitors.",{"@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/sunvozertinib-shining-light-on-lung-cancers-exon-20-fight/361722/",{"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/sunvozertinib-shining-light-on-lung-cancers-exon-20-fight/361722.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",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 exon 20 insertion mutations clinically challenging in NSCLC?","Question",{"text":112,"@type":113},"Exon 20 insertion mutations are generally resistant to first-generation EGFR-TKIs such as gefitinib or erlotinib, leading to poorer outcomes than classical EGFR mutations. Their molecular features reduce conventional inhibitor effectiveness.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How are Ex20ins typically detected, and what are the limitations of PCR-based testing?",{"text":117,"@type":113},"Comprehensive genomic testing using next generation sequencing is emphasized for accurately diagnosing diverse Ex20ins. PCR-based kits may miss as much as 40–50% of Ex20ins, and this risk also applies to other EGFR mutation subtypes with many variants.",{"name":119,"@type":110,"acceptedAnswer":120},"Do all Ex20ins show the same level of sensitivity to EGFR inhibitors?",{"text":121,"@type":113},"No. The commentary describes location-based heterogeneity: insertions near the αC helix are more sensitive, loop-region insertions are often insensitive, and near-loop versus far-loop insertions can show intermediate sensitivity. Some specific Ex20ins are reported as sensitive to osimertinib or other later-generation inhibitors, at least in vitro.","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},361722,1790656935,{"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":34,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","Editorial Commentary  \nSunvozertinib: shining light on lung cancer’s exon 20 fight  \nTetsuya Mitsudomi1,2^  \n1Izumi City General Hospital, Izumi, Osaka, Japan; 2Department of Innovative Medicine, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan  \nCorrespondence to: Tetsuya Mitsudomi, MD, PhD. President, Izumi City General Hospital, 4-5-1 Wake-cho, Izumi, Osaka 594-0073, Japan; Department of Innovative Medicine, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, [Japan. Email: mitsudom@gmail.com](Japan. Email: mitsudom@gmail.com).  \nComment on: Wang M, Fan Y, Sun M, et al. Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-smallcell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial. Lancet Respir Med 2024;12:217-224 .  \nKeywords: Non-small cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR); exon 20 insertion mutation; targeted therapy  \nSubmitted Oct 03, 2024. Accepted for publication Jan 17, 2025. Published online Feb 27, 2025.  \ndoi: 10.21037/tlcr-24-907  \nView this article at: [https://dx.doi.org/10.21037/tlcr-24-907](https://dx.doi.org/10.21037/tlcr-24-907)  \nNon-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR) gene usually demonstrates significant sensitivity to EGFR tyrosine kinase inhibitors (TKIs), exemplifying a prototype of precision medicine in cancer treatment. The most prevalent EGFR mutations are small deletions in exon 19 and leucine to arginine substitution at codon 858 (L858R), which are collectively referred to as classical EGFR mutations, accounting for 70–80% of all EGFR mutations. However, a range of rarer mutations exists, such as G719X, S768I, L747P/S, E709_T710delinsD, referred to as uncommon EGFR mutations and exon 20 insertion mutations (Ex20ins) (1) . Ex20ins mutations were originally described by two groups including ours (2,3), and later, it turned out that they account for about 10% of the EGFR mutations (1,4,5) . Although over 100 distinct Ex20ins have been identified (6), A767_V769 dup1, S768_D770dup, and N771 _H773dup collectively comprise more than 45% of the 636 Ex20ins according to the compilation of the five databases (6) . Thus, it is crucial to efficiently diagnose the diverse range of Ex20ins without missing any of them, as polymerase chain reaction (PCR)-based kits may miss as  \nhigh as 40–50% of Ex20ins (6,7) . This is also true for the EGFR exon 19 deletion as there are many variants for this subtype, too (8) as well as other driver genes (ALK/RET/ ROS1, etc.) (9) . The timely use of comprehensive genomic testing using a next generation sequencing is shown to prolong overall survival and to avoid ineffective and costly treatment (9) On the other hand, when considering the next-generation sequencing, we have to also be aware of several pitfalls related to tissue sample quality and quantity, or cost and accessibility (10) .  \nGr eulich et al. were the first to experimentally demonstrate that the Ex20ins, D770 _ 771ins NPG has a strong transforming capacity (11) . Yet, it is unresponsive to first-generation EGFR-TKI, such as gefitinib orerlotinib. Yasuda et al. characterized specifically Ex20ins for the first time and found that D770 _ 771ins NPG hasan unaltered adenosine triphosphate-binding pocket and the inserted residues form a wedge at the end of the C helix that promotes the active kinase conformation without enhancing affinity to EGFR TKI, resulting in insensitivity to the conventional EGFR-TKIs (12) . However, there is heterogeneity in the degree of insensitivity within Ex20ins  \n^ ORCID: 0000-0001-9860-8505.  \n1 A767 _V769dup, where dup is short for duplication, represents a change in amino acid sequence from …MASVDNPHV… to MASVASVDNP   Please note that this mutation can also be described either as M766_A767insASV or V769_D770insASV. Be aware that all these three represent the same mutat","cbCaig38iMyAnOKu","https://ap.wps.com/l/cbCaig38iMyAnOKu","pdf",373875,"English","# Editorial Commentary\n## Targeting EGFR Exon 20 Insertion in NSCLC\n## Detection Challenges and Need for Comprehensive Genomic Testing\n## Mechanisms of EGFR-TKI Insensitivity and Mutation Heterogeneity\n## Sensitivity to Later-Generation EGFR Inhibitors","[{\"question\":\"Why are EGFR exon 20 insertion mutations clinically challenging in NSCLC?\",\"answer\":\"Exon 20 insertion mutations are generally resistant to first-generation EGFR-TKIs such as gefitinib or erlotinib, leading to poorer outcomes than classical EGFR mutations. Their molecular features reduce conventional inhibitor effectiveness.\"},{\"question\":\"How are Ex20ins typically detected, and what are the limitations of PCR-based testing?\",\"answer\":\"Comprehensive genomic testing using next generation sequencing is emphasized for accurately diagnosing diverse Ex20ins. PCR-based kits may miss as much as 40–50% of Ex20ins, and this risk also applies to other EGFR mutation subtypes with many variants.\"},{\"question\":\"Do all Ex20ins show the same level of sensitivity to EGFR inhibitors?\",\"answer\":\"No. The commentary describes location-based heterogeneity: insertions near the αC helix are more sensitive, loop-region insertions are often insensitive, and near-loop versus far-loop insertions can show intermediate sensitivity. Some specific Ex20ins are reported as sensitive to osimertinib or other later-generation inhibitors, at least in vitro.\"}]","Sunvozertinib: shining light on lung cancer’s exon 20 fight | PDF",1790145383,18]