2. Academic Validation
  3. Glimepiride overcomes acquired resistance to EGFR TKIs in lung cancer via the AMPK/ERK/MMP7 signaling pathway

Glimepiride overcomes acquired resistance to EGFR TKIs in lung cancer via the AMPK/ERK/MMP7 signaling pathway

  • Biochem Pharmacol. 2025 Jul 12:241:117162. doi: 10.1016/j.bcp.2025.117162.
Hu Zhang 1,  Min Li 1,  Yan Li 1,  Yi Han 1,  Xin Huang 2,  Ling Li 3
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China.
  • 2 Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China. Electronic address: 13791120711@163.com.
  • 3 Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China. Electronic address: lilingfah@sdfmu.edu.cn.
PMID: 40659128 DOI: 10.1016/j.bcp.2025.117162
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.

Keywords

AMPK; Acquired resistance; EGFR TKIs; Glimepiride; MMP7.

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