Advancing small cell lung cancer metastasis research: innovations in preclinical mouse models

Small cell lung cancer (SCLC) represents one of the most aggressive malignancies, featured with its extraordinary metastatic capacity. Preclinical mouse models have become indispensable systems for studying the molecular mechanisms underlying SCLC metastasis. This review summarizes recent advances in genetically engineered mouse models (GEMMs) and transplantation models for SCLC metastasis research, highlighting their unique advantages in investigating oncogenic drivers, tumor heterogeneity, immune interactions, and therapeutic responses. We further discuss emerging technologies capable of integrating with these models to advance both mechanistic and translational research. Lineage tracing and multi-omics approaches have provided unprecedented resolution in mapping clonal dynamics and phenotypic plasticity during SCLC metastasis. High-throughput in vivo screening has accelerated the systematic identification of novel metastasis regulators, and humanized mouse models offer clinically relevant systems for investigating human-specific tumor-immune interactions and supporting preclinical evaluation of immunotherapies. Collectively, these preclinical systems are reshaping our understanding of SCLC metastasis and providing powerful platforms to guide therapeutic discovery.