GW3965 + gefitinib

GW3965 + gefitinib is an experimental combination therapy consisting of GW3965, a synthetic agonist of liver X receptors (LXR), and gefitinib, a small molecule tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR). This combination has been studied primarily in the context of non-small cell lung cancer (NSCLC) with acquired resistance to EGFR inhibitors. Preclinical studies demonstrate that co-administration leads to synergistic inhibition of cell proliferation and induction of apoptosis in NSCLC cells resistant to gefitinib. Mechanistically, this effect is mediated by downregulation of vimentin expression (a marker associated with epithelial-to-mesenchymal transition and drug resistance), inhibition of NF-κB signaling, modulation of AMPK/Akt/mTOR pathways, and reversal of autophagy-related resistance mechanisms[1][2][3][5]. The combination aims to overcome or reverse acquired resistance to EGFR-targeted therapies.