EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer.

摘要: Despite the success of treating EGFR-mutant lung cancer patients with EGFR tyrosine kinase inhibitors (TKI), all eventually acquire resistance to these therapies. Although various mechanisms have been described, there are currently no FDA-approved therapies that target alternative treat tumors acquired first-line TKI agents. Here we found EPHA2 is overexpressed in TKI-resistant tumor cells. Loss reduced viability erlotinib-resistant cells harboring EGFR(T790M) mutations vitro and inhibited growth progression an inducible EGFR(L858R+T790M)-mutant model vivo. Targeting decreased S6K1-mediated phosphorylation cell death agonist BAD, resulting proliferation increased apoptosis. Furthermore, pharmacologic inhibition by small-molecule inhibitor ALW-II-41-27 both survival was also effective decreasing third-generation AZD9291. Collectively, data define a role for maintenance TKI-resistant, indicate may serve as useful therapeutic tumors.