Rauner Gat, Gupta Piyush B, Kuperwasser Charlotte
Department of Developmental, Molecular & Chemical Biology, Tufts Graduate School of Biomedical Sciences, Boston, MA, USA.
Laboratory for the Convergence of Biomedical, Physical, and Engineering Sciences, Tufts University School of Medicine, Boston, MA, USA.
Nat Methods. 2025 Jul 25. doi: 10.1038/s41592-025-02769-1.
In vitro tumor models are essential tools for cancer research, offering key insights into not only tumor biology but also therapeutic responses. The transition from traditional two-dimensional to three-dimensional organoid systems marks a paradigm shift in cancer modeling. Although two-dimensional models have been instrumental in elucidating fundamental molecular and genetic mechanisms, they fail to accurately replicate the intricate three-dimensional architecture and dynamic microenvironment characteristic of human tumors. Here we outline how advanced organoid technologies now enable more faithful recapitulation of tumor heterogeneity that better mimic native tissue mechanics and biochemistry. We discuss emerging methods, including air-liquid interface cultures, microfluidic tumor-on-a-chip devices and high-content imaging integrated with machine learning, which collectively address longstanding challenges such as matrix variability and the limited incorporation of immune and vascular elements. These innovations promise to enhance reproducibility and scalability while providing unprecedented insights into tumor biology, cancer progression and therapeutic strategies.
体外肿瘤模型是癌症研究的重要工具，不仅能为肿瘤生物学提供关键见解，还能为治疗反应提供重要信息。从传统的二维模型向三维类器官系统的转变标志着癌症建模的范式转变。尽管二维模型在阐明基本分子和遗传机制方面发挥了重要作用，但它们无法准确复制人类肿瘤复杂的三维结构和动态微环境特征。在此，我们概述了先进的类器官技术如何能够更忠实地再现肿瘤异质性，更好地模拟天然组织的力学和生物化学特性。我们讨论了新兴方法，包括气液界面培养、微流控芯片肿瘤装置以及与机器学习相结合的高内涵成像，这些方法共同解决了长期存在的挑战，如基质变异性以及免疫和血管成分整合有限的问题。这些创新有望提高可重复性和可扩展性，同时为肿瘤生物学、癌症进展和治疗策略提供前所未有的见解。
