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Article Abstract
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) limits their clinical efficacy. Intratumoral heterogeneity and the coexistence of diverse resistance mechanisms make combination therapies focused on single molecules or pathways clinically ineffective. Here, our study demonstrated that glimepiride, a sulfonylurea drug, reversed and delayed acquired resistance to EGFR TKIs in lung cancer. Furthermore, glimepiride not only enhanced apoptosis in resistant cells but also suppressed cancer stemness. Mechanistically, glimepiride exerted these effects through AMPK activation, leading to subsequent suppression of the ERK/MMP7 signaling pathway. Our findings identify glimepiride as a promising therapeutic candidate for combination regimens in lung cancer treatment.
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| http://dx.doi.org/10.1016/j.bcp.2025.117162 | DOI Listing |
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