TY  - JOUR
AU  - Sagerer, Andre
AU  - Eyüpoglu, Ilker Y
AU  - Juratli, Tareq A
AU  - Cordes, Nils
TI  - Context-specific targeting of focal adhesion kinase in brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma.
JO  - Frontiers in oncology
VL  - 15
SN  - 2234-943X
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2026-00042
SP  - 1724278
PY  - 2025
AB  - 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.
KW  - FAK inhibitor (Other)
KW  - NF2-mutant meningioma (Other)
KW  - focal adhesion kinase (Other)
KW  - glioblastoma (Other)
KW  - pFAK-Y397 (Other)
KW  - precision oncology (Other)
KW  - synthetic lethality (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41487565
C2  - pmc:PMC12757307
DO  - DOI:10.3389/fonc.2025.1724278
UR  - https://inrepo02.dkfz.de/record/307537
ER  -