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In contrast, neurofibromatosis type 2 (NF2)-mutant meningiomas show a context-specific vulnerability: loss of merlin creates a synthetic lethal dependency on FAK signaling. Early-phase trials report promising control with favorable safety.",{"@graph":69,"@context":123},[70,84,106],{"@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/context-specific-targeting-of-focal-adhesion-kinase-in-brain-tumors-lessons-from-glioblastoma-and-neurofibromatosis-type-2-mutant-meningioma/417741/",{"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/context-specific-targeting-of-focal-adhesion-kinase-in-brain-tumors-lessons-from-glioblastoma-and-neurofibromatosis-type-2-mutant-meningioma/417741.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why did FAK inhibition fail to benefit glioblastoma patients despite strong target rationale?","Question",{"text":113,"@type":114},"Clinical trials did not show benefit, illustrating that target expression or known pathway involvement does not guarantee functional dependency required for therapeutic efficacy.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What creates the vulnerability of NF2-mutant meningiomas to FAK targeting?",{"text":118,"@type":114},"Loss of the tumor suppressor merlin (in NF2-mutant meningiomas) produces a synthetic lethal dependency on FAK signaling, making the target therapeutically meaningful in that context.",{"name":120,"@type":111,"acceptedAnswer":121},"How does the review connect biological context to precision oncology decisions?",{"text":122,"@type":114},"It contrasts GBM versus NF2-mutant meningiomas to argue that therapeutic targeting must be guided by context-specific functional dependency, not by target presence alone, aligning with a functional oncogenomics approach.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},417741,1790792919,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"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,"preview_page_count":4},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","TYPE Mini Review  \nPUBLISHED 19 December 2025 DOI 10.3389/fonc.2025.1724278  \nOPEN ACCESS  \nEDITED BY  \nRaphael Bertani,  \nUniversity of São Paulo, Brazil  \nREVIEWED BY  \nYogendra Nayak, Manipal University, India Hassan Mumtaz,  \nResear-Ligent Limited, United Kingdom Sixuan Pan,  \nUniversity of California, San Francisco, United States  \nDeeptarup Biswas,  \nHarvard Medical School, United States Cecilia Krona,  \nUppsala University, Sweden  \n*CORRESPONDENCE  \nAndre Sagerer  \n [andrenorbertjosef.sagerer@ukdd.de](andrenorbertjosef.sagerer@ukdd.de)  \nRECEIVED 13 October 2025  \nREVISED 03 December 2025  \nACCEPTED 08 December 2025  \nPUBLISHED 19 December 2025  \nCITATION  \nSagerer A, Eyüpoglu IY, Juratli TA and Cordes N (2025) Context-specific targeting of focal adhesion kinasein brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma.  \nFront. Oncol. 15:1724278 .  \ndoi: 10.3389/fonc.2025.1724278  \nCOPYRIGHT  \n© 2025 Sagerer, Eyüpoglu, Juratli and Cordes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nContext-specific targeting of focal adhesion kinase in brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma  \nAndre Sagerer 1,2*, Ilker Y. Eyüpoglu 1,2, Tareq A. Juratli 1,2 and Nils Cordes 2,3,4,5,6  \n1 Department of Neurosurgery, Medical Faculty and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany, 2 National Center for Tumor Diseases (NCT), NCT/UCC Dresden, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany, 3OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, 4 HelmholtzZentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany, 5German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany, 6 Department of Radiotherapy and Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany  \nFocal adhesion kinase (FAK) has long been explored as a therapeutic target in glioblastoma (GBM) based on its overexpression and involvement in invasive signaling. However, clinical trials have consistently failed to show benefit highlighting a core principle of translational oncology: target presence alone does not imply therapeutic relevance. In contrast, neurofibromatosis type 2 (NF2)-mutant meningiomas present a biologically grounded vulnerability, in which loss of the tumor suppressor moesin-ezrin-radixin-like protein (merlin) creates a synthetic lethal dependency on FAK. This context-specific dependency enables clinically meaningful targeting. Early-phase trials already show promising disease control with favorable safety profiles. This mini review examines the contrasting roles of FAK in GBM and NF2-mutant meningiomas to underscore the importance of biological context in therapeutic decisions. We propose that NF2-mutant meningiomas represent a model for context-specific, synthetic lethal targeting, exemplifying a functional oncogenomics approach to precision oncology.  \nKEYWORDS  \nFAK inhibitor, focal adhesion kinase, glioblastoma, NF2-mutant meningioma, pFAKY397, precision oncology, synthetic lethality  \nFrontiers in Oncology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nTranslational oncology often faces a fundamental challenge: therapeutic targets are frequently chosen based on ","cbCaijBM0CYq0aWr","https://ap.wps.com/l/cbCaijBM0CYq0aWr","pdf",1360453,"English","# Introduction\n## Translational oncology challenge in target selection\n## Distinct biological drivers across brain tumor entities\n# NF2 pathway and merlin loss\n## Frequency across WHO grades and anatomical enrichment\n## Synthetic lethal FAK dependency in NF2-mutant meningiomas","[{\"question\":\"Why did FAK inhibition fail to benefit glioblastoma patients despite strong target rationale?\",\"answer\":\"Clinical trials did not show benefit, illustrating that target expression or known pathway involvement does not guarantee functional dependency required for therapeutic efficacy.\"},{\"question\":\"What creates the vulnerability of NF2-mutant meningiomas to FAK targeting?\",\"answer\":\"Loss of the tumor suppressor merlin (in NF2-mutant meningiomas) produces a synthetic lethal dependency on FAK signaling, making the target therapeutically meaningful in that context.\"},{\"question\":\"How does the review connect biological context to precision oncology decisions?\",\"answer\":\"It contrasts GBM versus NF2-mutant meningiomas to argue that therapeutic targeting must be guided by context-specific functional dependency, not by target presence alone, aligning with a functional oncogenomics approach.\"}]","Context-specific targeting of focal adhesion kinase in brain tumors - lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma | PDF",1790610370,25]