<p>Cancer remains a leading cause of mortality worldwide, with its management challenged by profound biological complexity and substantial intratumoral and interpatient heterogeneity. Conventional preclinical tumor models fail to recapitulate key features of the human tumor microenvironment, limiting their translational relevance. Tumor organoids are three-dimensional (3D) culture systems that retain patient-specific tissue architecture and heterogeneity, and have emerged as powerful platforms for translational cancer therapy research. Recent advances in organoid engineering, including microfluidic organoid-on-chip systems, 3D bioprinting, and next-generation biomaterials, have markedly improved physiological relevance, experimental controllability, and scalability. These innovations enable higher-throughput drug screening and more informative functional profiling to support individualized therapeutic decision-making. In parallel, organoid-based predictive modeling frameworks are creating new opportunities to rationally design precision treatment regimens and to elucidate mechanisms underlying therapeutic response and acquired resistance. Importantly, integrating organoid-derived functional readouts with molecular and clinical data is accelerating bench-to-bedside translation and strengthening the evidence base for personalized oncology. Here, we systematically summarize the multidimensional applications of organoids in translational cancer therapy, critically discuss their advantages and current limitations, and outline key directions for future development, with the aim of facilitating the implementation and optimization of precision oncology.</p>

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Organoids in cancer therapy: translational applications and clinical promise

  • Mingzhen Bai,
  • Maoyun Liu,
  • Sheng Wang,
  • Ming Ran,
  • Jingyuan Ye,
  • Yuqin Xie,
  • Cheng Zhang,
  • Yi Wang,
  • Jiale Lu,
  • Fengsheng Dai,
  • Dewei Li,
  • Hui Li

摘要

Cancer remains a leading cause of mortality worldwide, with its management challenged by profound biological complexity and substantial intratumoral and interpatient heterogeneity. Conventional preclinical tumor models fail to recapitulate key features of the human tumor microenvironment, limiting their translational relevance. Tumor organoids are three-dimensional (3D) culture systems that retain patient-specific tissue architecture and heterogeneity, and have emerged as powerful platforms for translational cancer therapy research. Recent advances in organoid engineering, including microfluidic organoid-on-chip systems, 3D bioprinting, and next-generation biomaterials, have markedly improved physiological relevance, experimental controllability, and scalability. These innovations enable higher-throughput drug screening and more informative functional profiling to support individualized therapeutic decision-making. In parallel, organoid-based predictive modeling frameworks are creating new opportunities to rationally design precision treatment regimens and to elucidate mechanisms underlying therapeutic response and acquired resistance. Importantly, integrating organoid-derived functional readouts with molecular and clinical data is accelerating bench-to-bedside translation and strengthening the evidence base for personalized oncology. Here, we systematically summarize the multidimensional applications of organoids in translational cancer therapy, critically discuss their advantages and current limitations, and outline key directions for future development, with the aim of facilitating the implementation and optimization of precision oncology.