A Urokinase Receptor–Bim Signaling Axis Emerges during EGFR Inhibitor Resistance in Mutant EGFR Glioblastoma

Abstract excerpt

EGFR is the most common genetically altered oncogene in glioblastoma (GBM), but small-molecule EGFR tyrosine kinase inhibitors (TKI) have failed to yield durable clinical benefit. Here, we show that in two novel model systems of acquired resistance to EGFR TKIs, elevated expression of urokinase plasminogen activator (uPA) drives signaling through the MAPK pathway, which results in suppression of the proapoptotic...

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