NIH R01 · 2024
Targeting the HGF-MET-TWIST1 pathway to overcome EGFR TKI resistance
Epidermal Growth Factor Receptor (EGFR) mutant (mt) non-small cell lung cancer (NSCLC), initially has a high response rate to EGFR tyrosine kinase inhibitors (TKIs), however, resistance is inevitable. HGF-MET pathway activation and an epithelial-mesenchymal transition (EMT) transcription factor (TF) induced mesenchymal phenotype are commonly observed mechanisms of EGFR TKI resistance. We have identified the hepatocyte growth factor (HGF)-MET-TWIST1 axis as a novel targetable signaling axis that may account for both de novo and acquired resistance to EGFR TKIs including osimertinib. Our published data showed that the EMT-TF, TWIST1 is required for EGFR mt tumorigenesis and can mediated EGFR…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.