Open access
Understanding tumor adaptations and resistance to MET inhibitors in MET-altered non-small cell lung cancer
M. Simard
E. Marin
S. García-Román
C. Aguado
Michail Yekelchyk
Carolin Schmelas
Nina Berges
Balca R. Mardin
Sophie Ockfen
Rebecca Schaefer
Markus Esser
Jing Yang
Felix Geist
O. Schadt
C. Reusch
Sebastian Bender
N. Jordana-Ariza
C. Esparré
Ruth Román
Tolulope Apata
Cristina Teixidó
M. Rico-Pastó
Sara Hijazo-Pechero
M. Querol
M. Morfouace
M. Molina-Vila
Noemí Reguart
Niki Karachaliou
Medicine
Abstract
Highlights • MET inhibitor resistance is heterogeneous across distinct MET-altered NSCLC.• Spatial transcriptomics reveal shared ECM remodeling in tumors upon progression.• In vitro models partially recapitulate aspects of clinical MET inhibitor resistance.• CRISPR and combination drug screens reveal overlapping functional dependencies.• Dual targeting of EGFR/MAPK/PI3K with MET restores sensitivity in resistance settings.