Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer.

ABSTRACT: Objective: To investigate the preclinical efficacy and identify predictive biomarkers of polo-like kinase 1 (PLK1) inhibitors in small cell lung cancer (SCLC) models. Methods: We tested the cytotoxicity of selective PLK1 inhibitors (rigosertib, volasertib, and onvansertib) in a panel of SCLC cell lines. We confirmed the therapeutic efficacy of subcutaneous xenografts of representative cell lines and in four patient-derived xenograft models generated from patients with platinum-sensitive and platinum-resistant SCLC. We employed an integrated analysis of genomic and transcriptomic sequencing data to identify potential biomarkers of the activity and mechanisms of resistance in laboratory-derived resistance models. Results: Volasertib, rigosertib, and onvansertib showed st

SUBMITTER: Zhang G 

PROVIDER: S-EPMC11815996 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature