A comprehensive review of microfluidic-based organ-on-chip technology in the application of preclinical drug discovery studies.

Microfluidic organ-on-chip (OoC) technologies have emerged as reliable platforms for the physiologically accurate simulation of human tumours by precisely modulating cellular, biochemical, and biomechanical parameters. This review critically examines recent advancements in organ-on-chip (OoC) systems for applications in precision oncology, immuno-oncology, preclinical drug discovery, therapeutic response assessment, and mechanistic studies of therapeutic resistance. Unlike traditional preclinical models, OoC systems integrate patient-derived tumour tissues, stromal and immunological components, and three-dimensional microenvironments to more accurately reflect tumour heterogeneity and therapeutic response. We further explored how these technologies enable the real-time evaluation of drug sensitivity, immunological interactions, hypoxia-driven adaptability, and stroma-mediated resistance, providing functional insights beyond genetic profiling. By incorporating recent developments in patient-derived models, immunooncology, mechanobiology, and clinically relevant drug response prediction, this review underscores the translational and mechanistic significance of OoC technologies, distinguishing it from previous reviews that primarily focused on microfabrication and device engineering. We also address contemporary challenges related to standardisation, regulatory validation, scalability, and reproducibility. Collectively, OoC technologies hold significant potential to advance precision medicine, enhance translational oncology, and reduce reliance on animal models in cancer research.