Microtubule Inhibitors Induce Cross-Resistance to Osimertinib Through CaMKII Activation in EGFR-Mutated NSCLC.

ABSTRACT: The current standard postoperative adjuvant therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) includes chemotherapy, including microtubule inhibitors prior to the administration of osimertinib, an EGFR-tyrosine kinase inhibitor (TKI). However, multidrug resistance following treatment with microtubule inhibitors has been reported, and the optimal sequence of drug administration for EGFR-mutated NSCLC remains undefined. In this study, we investigated whether prior treatment with microtubule inhibitors induces acquired cross-resistance to osimertinib in EGFR-mutated NSCLC cells in vitro. To model acquired resistance, PC-9 cells were exposed to vinorelbine or paclitaxel for 18 weeks-approximating the clinical duration of four adjuvant

SUBMITTER: Kono K 

PROVIDER: S-EPMC12861095 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature