Advancing Preclinical Oncology: Next‐Generation Mouse Models for Decoding Tumor Progression and Metastasis

ABSTRACT Next‐generation mouse models have transformed preclinical oncology by enabling detailed study of tumor initiation, progression, immune interactions, and metastasis. Traditional systems lacked tumor heterogeneity and immune relevance. Advanced platforms such as genetically engineered mouse models (GEMMs), humanized mice, patient‐derived xenografts (PDXs), and organoid‐based models provide genetic accuracy, patient‐specific biology, and functional immune environments. Recent developments, such as intravital imaging, lineage tracing, multi‐omics, and artificial intelligence (AI), have further improved the understanding of tumor dynamics and therapeutic response. Notwithstanding these major improvements, there are no currently available mouse models that can effectively recapitulate the complexity, latency, organ‐specific spread, and tumor–microenvironment interactions that are seen in human metastasis. This means that there is a need for further optimization and enhancement of the preclinical models to make them more translatable and relevant. Together, these new‐generation models offer a unique opportunity for the transition from experimental research to clinical oncology and for precision medicine and metastasis‐oriented cancer research.