Combining mechanistic quantitative systems pharmacology modeling and patient-derived organoid testing in MET-aberrant non-small cell lung cancer for high-throughput combination efficacy analysis and personalized treatment design.

ABSTRACT: Non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations or MET overexpression/amplification typically exhibits highly proliferative and invasive phenotypes and is a significant threat to human health. Although tyrosine kinase inhibitors targeting MET have been approved for clinical use over the past decade, treatment for MET-aberrant patients still face large unmet needs with issues such as limited response duration and drug resistance, low response rates and need for effective combination therapies, differential treatment response in patient subgroups, as well as clinical dose optimization and possibility of personalized medicine. To address these challenges, we developed a quantitative systems pharmacology (QSP) model that mechanistically recapitulated the complex reg

SUBMITTER: Hu J 

PROVIDER: S-EPMC12682884 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature