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@ARTICLE{Sagerer:307537,
author = {A. Sagerer and I. Y. Eyüpoglu and T. A. Juratli and N.
Cordes$^*$},
title = {{C}ontext-specific targeting of focal adhesion kinase in
brain tumors: lessons from glioblastoma and
neurofibromatosis type 2-mutant meningioma.},
journal = {Frontiers in oncology},
volume = {15},
issn = {2234-943X},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2026-00042},
pages = {1724278},
year = {2025},
abstract = {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.},
subtyp = {Review Article},
keywords = {FAK inhibitor (Other) / NF2-mutant meningioma (Other) /
focal adhesion kinase (Other) / glioblastoma (Other) /
pFAK-Y397 (Other) / precision oncology (Other) / synthetic
lethality (Other)},
cin = {DD01},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41487565},
pmc = {pmc:PMC12757307},
doi = {10.3389/fonc.2025.1724278},
url = {https://inrepo02.dkfz.de/record/307537},
}