EGFR-TKI + metformin

EGFR-TKI + metformin is a combination therapy consisting of an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and the antidiabetic drug metformin. This regimen is primarily investigated for the treatment of non-small cell lung cancer (NSCLC) with activating EGFR mutations. The rationale for this combination stems from evidence that while EGFR-TKIs are effective in patients with sensitizing EGFR mutations, resistance often develops. Metformin has demonstrated synergistic antitumor effects when combined with EGFR-TKIs by reversing or delaying both primary and acquired resistance mechanisms. Mechanistically, the combination works through several pathways: - Metformin activates AMP-activated protein kinase (AMPK), which inhibits downstream ERK/NF-κB signaling implicated in TKI resistance. - It impairs TGF-β-induced epithelial-mesenchymal transition (EMT), reduces IL-6 secretion, and inhibits IL-6R/JAK1/STAT3 signaling—processes associated with drug resistance. - In some models, it suppresses IGF-1R signaling to overcome primary resistance. Clinical studies have shown that adding metformin to an EGFR-TKI can improve progression-free survival and overall survival in NSCLC patients compared to TKI monotherapy[1][2][5]. The most commonly used TKIs in these combinations include gefitinib, erlotinib, and afatinib.

Other names

EGFR tyrosine kinase inhibitor + metforminEGFR-TKI and metforminepidermal growth factor receptor tyrosine kinase inhibitor plus metformin