[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332162-105":59,"doc-detail-332162-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","transforming-tumoroids-derived-from-alk-positive-pulmonary-adenocarcinoma-to-squamous-cell-carcinoma-in-vivo","Transforming tumoroids derived from ALK-positive pulmonary adenocarcinoma to squamous cell carcinoma in vivo","","Approximately 3–5% of non-small cell lung cancers (NSCLC) carry ALK fusion genes and may respond to ALK tyrosine kinase inhibitors, yet limited models exist for EML4-ALK variant 3 (v3) tumoroids suitable for long-term culture. This study established PDT-LUAD#119 tumoroids from an ALK fusion patient sample, achieving 12-month culture. Whole-exome and RNA sequencing identified TP53 mutations and EML4-ALKv3, and PDT-LUAD#119 showed sensitivity to multiple ALK TKIs. Xenografts unexpectedly developed ALK-positive squamous carcinoma with adenosquamous features, enabling mechanistic studies and preclinical evaluation.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/transforming-tumoroids-derived-from-alk-positive-pulmonary-adenocarcinoma-to-squamous-cell-carcinoma-in-vivo/332162/",{"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/transforming-tumoroids-derived-from-alk-positive-pulmonary-adenocarcinoma-to-squamous-cell-carcinoma-in-vivo/332162.png","ImageObject",300,407,{"name":92,"@type":93},"Violet","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What ALK-related mutation and culture duration were achieved in the established tumoroids?","Question",{"text":112,"@type":113},"The study established PDT-LUAD#119 tumoroids from a patient with an EML4-ALK fusion, achieving long-term culture for 12 months. Sequencing identified EML4-ALKv3 along with TP53 mutations.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did PDT-LUAD#119 tumoroids respond to ALK tyrosine kinase inhibitors?",{"text":117,"@type":113},"PDT-LUAD#119 lung tumoroids were sensitive to ALK TKIs including crizotinib, alectinib, entrectinib, and lorlatinib, mirroring sensitivity reported for EML4-ALK variant 1 (v1) NCI-H3122 cells.",{"name":119,"@type":110,"acceptedAnswer":120},"What transformation was observed in xenografts derived from PDT-LUAD#119 tumoroids?",{"text":121,"@type":113},"Clear squamous cell carcinoma and solid adenocarcinoma appeared in xenografts from PDT-LUAD#119, indicating adenosquamous carcinoma. Immunostaining showed ALK positivity in the squamous component, supporting squamous transformation of the adenocarcinoma.","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},332162,1790192586,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"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,"preview_page_count":4},4398048950312,"https://ap-avatar.wpscdn.com/avatar/400002538284de19e3c?_k=1778320343897328908","Human Cell (2024) 37:1132–1140  \n[https://doi.org/10.1007/s13577-024-01085-8](https://doi.org/10.1007/s13577-024-01085-8)  \nTransforming tumoroids derived from ALK‑positive pulmonary adenocarcinoma to squamous cell carcinoma in vivo  \nEtsuko Yokota1 · Miki Iwai2 · Yuta Ishida1 · Takuro Yukawa1 · Masaki Matsubara1 · Yoshio Naomoto1 · Hideyo Fujiwara3 · Yasumasa Monobe3,4 · Minoru Haisa5,6,7 · Nagio Takigawa2,8 · Takuya Fukazawa1,2 · Tomoki Yamatsuji1  \nReceived: 8 April 2024 / Accepted: 27 May 2024 / Published online: 3 June 2024 © The Author(s) 2024  \nAbstract  \nApproximately 3–5% of non-small cell lung cancers (NSCLC) harbor ALK fusion genes and may be responsive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. There are only a few reports on cell lines with EML4-ALK variant 3 (v3) and tumoroids that can be subject to long-term culture (> 3 months) . In this study, we established tumoroids (PDTLUAD\\#119) from a patient with lung cancer harboring EML4-ALK that could be cultured for 12 months. Whole-exome sequencing and RNA sequencing analyses revealed TP53 mutations and an EML4-ALKv3 mutation. PDT-LUAD\\#119 lung tumoroids were sensitive to the ALK tyrosine kinase inhibitors (ALK TKIs) crizotinib, alectinib, entrectinib, and lorlatinib, similar to NCI-H3122 cells harboring EML4-ALK variant 1 (v1) . Unexpectedly, clear squamous cell carcinoma and solid adenocarcinoma were observed in xenografts from PDT-LUAD\\#119 lung tumoroids, indicating adenosquamous carcinoma. Immunostaining revealed that the squamous cell carcinoma was ALK positive, suggesting a squamous transformation of the adenocarcinoma. Besides providing a novel cancer model to support basic research on ALK-positive lung cancer, PDTLUAD\\#119 lung tumoroids will help elucidate the pathogenesis of adenosquamous carcinoma.  \nKeywords Lung cancer · ALK fusion genes · Adenosquamous carcinoma · Preclinical cancer model · Tumoroids  \n* Takuya Fukazawa [fukazawat@aol.com](fukazawat@aol.com)  \n1 Department of General Surgery, Kawasaki Medical School, Okayama 700-8505, Japan  \n2 General Medical Center Research Unit, Kawasaki Medical School, Okayama, Japan  \n3 Department of Pathology, Kawasaki Medical School, Okayama, Japan  \n4 Okayama Medical Laboratories Co., Ltd., Kurashiki, Japan  \n5 Kawasaki Medical School General Medical Center, Okayama, Japan  \n6 Department of Medical Care Work, Kawasaki College of Health Professions, Okayama, Japan  \n7 Kawasaki Geriatric Medical Center, Okayama, Japan  \n8 Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan  \nIntroduction  \nIn recent years, the identification of lung cancers harboring rare driver mutations has increased, leading to a considerable increase in the number of approved targeted therapies. This approach has substantially improved the prognosis of patients with lung cancer [1] . Anaplastic lymphoma kinase (ALK) rearrangements are detected in 3–5% of all non-small cell lung cancers (NSCLCs), and ALK tyrosine kinase inhibitors (TKIs) improve the prognosis of patients with ALKpositive NSCLC [2] . EML4 is located on chromosome 2p21 and contains 26 exons. There are various fusion breakpoints in multiple exons of EML4 in EML4-ALK-positive lung cancer. Among these, EML4-ALK variant 1 (v1), where exons 20–29 ofALK fuse with exons 1–13 of EML4, and variant 3 (v3), where exons 20–29 ofALK fuse with exons 1–6 of EML4, are the most commonly observed variants, constituting approximately 75–80% of the total variants [3] . Furthermore, patients with lung cancer harboring EML4-ALKv3 or TP53 mutations have a poor prognosis [4, 5] .  \nIn recent years, organoid research has been conducted using pluripotent stem cells and biopsy and surgical specimens [6, 7] . In cancer research, organoids have emerged as novel preclinical models derived from various malignant tumors, serving as alternatives to traditional twodimensional cell cultures and genetically engineered mouse models [8] . In our previous studies,","cbCaiofuTzL1CBD4","https://ap.wps.com/l/cbCaiofuTzL1CBD4","pdf",2749168,"English","# Abstract\n# Introduction\n# Materials and methods\n## Cell lines and their culture conditions\n## Patient-derived tumoroid culture","[{\"question\":\"What ALK-related mutation and culture duration were achieved in the established tumoroids?\",\"answer\":\"The study established PDT-LUAD#119 tumoroids from a patient with an EML4-ALK fusion, achieving long-term culture for 12 months. Sequencing identified EML4-ALKv3 along with TP53 mutations.\"},{\"question\":\"How did PDT-LUAD#119 tumoroids respond to ALK tyrosine kinase inhibitors?\",\"answer\":\"PDT-LUAD#119 lung tumoroids were sensitive to ALK TKIs including crizotinib, alectinib, entrectinib, and lorlatinib, mirroring sensitivity reported for EML4-ALK variant 1 (v1) NCI-H3122 cells.\"},{\"question\":\"What transformation was observed in xenografts derived from PDT-LUAD#119 tumoroids?\",\"answer\":\"Clear squamous cell carcinoma and solid adenocarcinoma appeared in xenografts from PDT-LUAD#119, indicating adenosquamous carcinoma. Immunostaining showed ALK positivity in the squamous component, supporting squamous transformation of the adenocarcinoma.\"}]","Transforming tumoroids derived from ALK-positive pulmonary adenocarcinoma to squamous cell carcinoma in vivo | PDF",1789997128,23]