Organoid technology in cancer research

Organoid technology has emerged as a transformative tool in cancer research by recapitulating the structural complexity, genomic integrity, and phenotypic heterogeneity of human primary tumors. Over the past 15 years, this technology has transcended the limitations of traditional preclinical cancer models, evolving from a specialized developmental biology technique into a versatile platform that spans basic mechanistic research, translational drug development, and clinical personalized medicine. This review provides a comprehensive and in-depth overview of organoid systems, spanning fundamental biological principles, standardized methodologies for tumor organoid establishment, and multi-dimensional applications across the entire cancer research continuum. We highlight mechanistic insights into tumor initiation, clonal evolution, progression, and metastatic colonization revealed by organoid models, as well as translational advances in high-throughput drug discovery, functional precision oncology, immuno-oncology therapeutic development, and early cancer detection and interception. Particular emphasis is placed on therapeutic development strategies and recent prospective clinical trials validating patient-derived organoids (PDOs) as predictive functional biomarkers for treatment response, which represents the most critical translational milestone in the field. By integrating cutting-edge single-cell multi-omics technologies, spatial profiling, and bioengineering advances, we further discuss current limitations, unresolved technical and biological challenges, and future directions aimed at bridging the long-standing gap between bench research and clinical practice. This work aims to present an updated, clinically oriented synthesis of organoid applications in oncology, with the ultimate goal of accelerating the clinical translation of organoid technology to advance precision cancer care and improve patient outcomes.