Itraconazole Reversing Acquired Resistance to Osimertinib in NSCLC by Inhibiting the SHH/DUSP13B/p-STAT3 Axis.

ABSTRACT: There is an urgent necessity to devise efficient tactics to tackle the inevitable development of resistance to osimertinib, which is a third-generation epidermal growth factor receptor (EGFR) inhibitor used in treating EGFR-mutant nonsmall cell lung cancer (NSCLC). This study demonstrates that combining itraconazole with osimertinib synergistically reduces the proliferation and migration, enhances the apoptosis of osimertinib-resistant cells, and effectively inhibits the growth of osimertinib-resistant tumors. Mechanistically, itraconazole combined with osimertinib promotes the proteasomal degradation of sonic hedgehog (SHH), resulting in inactivation of the SHH/Dual-specificity phosphatase 13B (DUSP13B)/p-STAT3 and Hedgehog pathways, suppressing Myc proto-oncogene protein (c-Myc). Additio

SUBMITTER: Zheng H 

PROVIDER: S-EPMC11831513 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature