%0 Journal Article
%A Sagerer, Andre
%A Eyüpoglu, Ilker Y
%A Juratli, Tareq A
%A Cordes, Nils
%T Context-specific targeting of focal adhesion kinase in brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma.
%J Frontiers in oncology
%V 15
%@ 2234-943X
%C Lausanne
%I Frontiers Media
%M DKFZ-2026-00042
%P 1724278
%D 2025
%X 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.
%K FAK inhibitor (Other)
%K NF2-mutant meningioma (Other)
%K focal adhesion kinase (Other)
%K glioblastoma (Other)
%K pFAK-Y397 (Other)
%K precision oncology (Other)
%K synthetic lethality (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41487565
%2 pmc:PMC12757307
%R 10.3389/fonc.2025.1724278
%U https://inrepo02.dkfz.de/record/307537