Therefore, altogether our data provide new insights into proteome regulations in the context of overcoming the NSCLC resistance to gefitinib through KDACi in H358 KRAS mutated and amphiregulin-overexpressing NSCLC cells.
This study is aimed at finding the prognostic importance of EGFR rare mutations and serum EGFR, amphiregulin (AR), and TGF-α (Transforming Growth Factor-alpha) in NSCLC.
The objective of the current study was to evaluate the association between AR expression and the efficacy of using EGFR TKIs in the treatment of patients with WT EGFR-positive NSCLC.
Amphiregulin expression was significantly higher in NSCLC patients that developed stable disease compared with those that developed disease progression following gefitinib or erlotinib treatment.
Pretreatment of NSCLC cells with GRP resulted in an increase in the IC(50) of gefitinib of up to 9-fold; this protective effect was mimicked by the pretreatment of cells with amphiregulin and reversed by Akt or PI3K inhibition.
Our data suggest that the status of amphiregulin and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC.
Moreover, we proved that the anti-apoptotic activity of amphiregulin, a protein that was significantly over-expressed in non-responders but undetectable in responders, leads to resistance of NSCLC cells to gefitinib in vitro.
Moreover, we proved that the anti-apoptotic activity of amphiregulin, a protein that was significantly over-expressed in non-responders but undetectable in responders, leads to resistance of NSCLC cells to gefitinib in vitro.