Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition.

ABSTRACT: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) for treating advanced non-small cell lung cancer (NSCLC). However, drug resistance seriously impedes the clinical efficacy of gefitinib. This study investigated the repositioning of the non-oncology drug capable of inhibiting histone deacetylases (HDACs) to overcome gefitinib resistance. A few drug candidates were identified using the in silico repurposing tool "DRUGSURV" and tested for HDAC inhibition. Flunarizine, originally indicated for migraine prophylaxis and vertigo treatment, was selected for detailed investigation in NSCLC cell lines harboring a range of different gefitinib resistance mechanisms (EGFR T790M, KRAS G12S, MET amplification, or PTEN loss). The circumvention of gefitinib resistance by

SUBMITTER: To KKW 

PROVIDER: S-EPMC10580381 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature