Organ-on-a-Chip Technology for Personalized Cancer Treatment: Modeling Tumor Microenvironment Heterogeneity and Drug Response in Patient-Derived Organoids

Abstract

The emergence of organ-on-a-chip (OoC) technology represents a paradigm shift in cancer research and personalized medicine, offering unprecedented capabilities to recapitulate the complex tumor microenvironment (TME) and predict patient-specific therapeutic responses. This review comprehensively examines the integration of microfluidic platforms with patient-derived organoids to model tumor heterogeneity, stromal interactions, and pharmacological responses with physiological relevance. Traditional two-dimensional cell culture systems and animal models have demonstrated significant limitations in predicting clinical outcomes, with approximately 90% of oncology drugs failing during clinical trials despite promising preclinical results. Organ-on-a-chip platforms address these limitations by incorporating critical elements of the TME, including extracellular matrix composition, fluid dynamics, immune cell interactions, and oxygen gradients that fundamentally influence cancer progression and treatment efficacy. Recent advances in microfabrication, biomaterials engineering, and stem cell biology have enabled the development of sophisticated tumor-on-a-chip models that maintain patient-specific genetic and phenotypic characteristics while providing real-time monitoring capabilities. This technology facilitates high-throughput drug screening, biomarker discovery, and mechanistic investigations of therapy resistance mechanisms. The integration of multi-omics approaches with OoC platforms promises to accelerate the translation of precision oncology from bench to bedside, offering clinicians powerful tools for treatment selection and combination therapy optimization. This review discusses current technological capabilities, clinical applications, regulatory considerations, and future directions toward establishing organ-on-a-chip systems as standard platforms for personalized cancer treatment strategies.