Organoids as Next-Generation Models of Tumor Drug Resistance
Keywords:
Organoids, Drug resistance, 3D cultures, Microfluidic chip technologies, Preclinical models, Tumor microenvironment, Personalized medicineAbstract
Tumor drug resistance is a major clinical challenge and critical to patient outcomes. Although extensive studies on mechanisms and drug development using cell and animal models exist, clinical results remain limited or ineffective. Recently, organoids have emerged as a powerful model that closely reproduces the structural and genetic features of tumors in vivo, making them an increasingly valuable platform for investigating resistance mechanisms and developing new therapeutic strategies. We reviewed organoid applications in elucidating tumor drug-resistance mechanisms, advancing therapies, and supporting clinical research, underscoring their critical role in overcoming treatment resistance. These mechanisms include abnormal cancer-related signaling, interactions between tumor and microenvironmental cells, DNA repair, epigenetic changes, and modifications in tumor cell membrane proteins. As an emerging preclinical model, organoids help bridge the gap between basic research and clinical practice, supporting the development of strategies to reverse drug resistance. These strategies include designing new targeted drugs, testing the efficacy of combination therapies, repurposing existing drugs, and screening personalized treatments for rare tumors. Moreover, in clinical trials, organoids can help guide therapy selection and enable preclinical evaluation of emerging therapeutic strategies. Although organoids lack the full in vivo microenvironment and an intact vascular system, advances in co-culture platforms and microfluidic chip technologies are steadily overcoming these limitations. As organoids integrate with such innovations, their role in drug-resistance research will continue to grow.
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