Targeting PLK1 potentiates the antitumor efficacy of EGFR-TKIs through inhibiting the JAK1/STAT3 pathway.

ABSTRACT: Despite the rapid development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in recent decades, resistance remains a significant challenge in managing advanced non-small cell lung cancer (NSCLC). Elucidating the mechanisms underlying EGFR-TKI resistance and developing novel strategies are therefore crucial. In this study, we investigated the role of polo-like kinase 1 (PLK1) in EGFR-mutant NSCLC and evaluated the therapeutic potential of combining EGFR-TKIs with PLK1 inhibitors. We demonstrated that high PLK1 expression correlates with STAT3 signaling activation and decreased survival probability in EGFR-mutant NSCLC patients. Subsequent studies revealed that PLK1 inhibitors effectively reversed the activation of STAT3 induced by EGFR-TKIs. When used in combinat

SUBMITTER: Li C 

PROVIDER: S-EPMC12808168 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature