MINI REVIEW article
Front. Oncol.
Sec. Neuro-Oncology and Neurosurgical Oncology
This article is part of the Research TopicInnovative Strategies in Overcoming Glioblastoma: Advancements in Treatment and ResearchView all 15 articles
Context‑specific targeting of focal adhesion kinase in brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma
Provisionally accepted
- 1Department of Neurosurgery, Medical Faculty and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Fetscherstraße 74, 01307, Dresden, Germany
- 2National Center for Tumor Diseases Dresden (NCT/UCC), partnership of DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, 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, 01307, Dresden, Germany
- 4Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology - OncoRay, 01328, Dresden, Germany
- 5German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), 69192, Dresden, Germany
- 6Department of Radiotherapy and Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Focal 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.
Keywords: FAK inhibitor, focal adhesion kinase, Glioblastoma, NF2-mutant meningioma, pFAK-Y397, precision oncology, synthetic lethality
Received: 13 Oct 2025; Accepted: 08 Dec 2025.
Copyright: © 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) or licensor 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.
* Correspondence: Andre Sagerer
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.