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Ex vivo drug screening across 160 anti-cancer therapies is integrated with gene panel sequencing and histology to link drug sensitivity with molecular features, including driver mutations and genomic vulnerabilities.",{"@graph":14,"@context":72},[15,34,55],{"@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/research-report/","Research & 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sensitivity and molecular features connected in the study?",{"text":71,"@type":63},"Functional drug screen results for 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses to associate sensitivity with molecular characteristics, including driver mutations.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},342658,1790146441,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & 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[homepage:](homepage: www.elsevier.com/locate/tranon)[ www.elsevier.com/locate/tranon](homepage: www.elsevier.com/locate/tranon)  \nOriginal Research  \nAssessment of targeted therapy opportunities in sinonasal cancers using patient-derived functional tumor models  \nNoora Lehtinena, Janne Suhonena, Kiesha Ricea, Eetu V¨alim¨aki a, Mervi Toriseva b, c, Johannes Routilab, d, Perttu Halme b, d, Melissa Rahie, f, Heikki Irjalab, d, Ilmo Leivob, g, Markku Kallajoki g, Matthias Nees b, c, h, Teijo Kuopio i,j, Sami Ventel¨a b, c, d, \\#,  \nJuha K. Rantalaa, \\#, *  \na Misvik Biology Oy, Turku, Finland  \nb Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland c FICAN West Cancer Centre, Turku, Finland  \nd Department for Otorhinolaryngology-Head and Neck Surgery, University of Turku and Turku University Hospital, Turku, Finland  \ne Department of Neurosurgery, Neurocenter, Turku University Hospital, Turku, Finland f Clinical Neurosciences, University of Turku, Turku, Finland  \ng Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland h Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland i Department of Biological and Environmental Science, University of Jyv¨askyl¨a, Jyv¨askyl¨a, Finland j Wellbeing Services County of Central Finland, Jyv¨askyl¨a, Finland  \nA R T I C L E I N F O  \nKeywords:  \nSinonasal cancer Ex vivo drug screening Driver mutation Targeted therapy  \nA B S T R A C T  \nMalignant tumors derived from the epithelium lining the nasal cavity region are termed sinonasal cancers, a highly heterogeneous group of rare tumors accounting for 3 – 5 % of all head and neck cancers. Progress with next-generation molecular profiling has improved our understanding of the complexity of sinonasal cancers and resulted in the identification of an increasing number of distinct tumor entities. Despite these significant developments, the treatment of sinonasal cancers has hardly evolved since the 1980s, and an advanced sinonasal cancer presents a poor prognosis as targeted therapies are usually not available. To gain insights into potential targeted therapeutic opportunities, we performed a multiomics profiling of patient-derived functional tumor models to identify molecular characteristics associated with pharmacological responses in the different subtypes of sinonasal cancer.  \nMethods: Patient-derived ex vivo tumor models representing four distinct sinonasal cancer subtypes: sinonasal intestinal-type adenocarcinoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma and SMARCB1 deficient sinonasal carcinoma were included in the analyses. Results of functional drug screens of 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses of the tumor tissues and the ex vivo cell cultures to establish associations between drug sensitivity and molecular characteristics including driver mutations.  \nResults: The different sinonasal cancer subtypes display considerable differential drug sensitivity. Underlying the drug sensitivity profiles, each subtype was associated with unique molecular features. The therapeutic vulnerabilities correlating with specific genomic background were extended and validated with in silico analyses of cancer cell lines representing different human cancers and with reported case studies of sinonasal cancers treated with targeted therapies.  \nAbbreviations: BSA, bovine serum albumin; CCLE, Cancer Cell Line Encyclopedia; CK, cytokeratin; GR, growth rate; HDAC, histone deacetylase; IHC, immunohistochemical; ITAC, intestinal-type adenocarcinoma; MSI, microsatellite instability; NGS, next-generation sequencing; RT, room temperature; SDSC, SMARCB1 deficient sinonasal carcinoma; SNC, sinonasal cancer; SNEC, sinonasal neuroendocrine carcinoma; SNSCC, squ","cbCaicMoZSn4uSDK","https://ap.wps.com/l/cbCaicMoZSn4uSDK","pdf",6413243,"English","# Abstract\n## Methods\n## Results\n## Conclusion\n## Introduction","[{\"question\":\"What was the main goal of this research?\",\"answer\":\"To identify targeted therapeutic opportunities in sinonasal cancers by linking drug-response profiles to molecular characteristics in patient-derived functional tumor models.\"},{\"question\":\"What types of tumor models and subtypes were included?\",\"answer\":\"Four ex vivo patient-derived tumor model subtypes were analyzed: sinonasal intestinal-type adenocarcinoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, and SMARCB1-deficient sinonasal carcinoma.\"},{\"question\":\"How were drug sensitivity and molecular features connected in the study?\",\"answer\":\"Functional drug screen results for 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses to associate sensitivity with molecular characteristics, including driver mutations.\"}]","Assessment of targeted therapy opportunities in sinonasal cancers using patient-derived functional tumor models | PDF",1790047587,23]