Existing organoid models fall short of fully capturing the complexity of cancer because they lack sufficient multicellular diversity, tissue-level organization, biological durability and experimental flexibility. Thus, many multifactorial cancer processes, especially those involving the tumor microenvironment, are difficult to study ex vivo. To overcome these limitations, we herein implemented tissue-engineering and microfabrication technologies to develop topobiologically complex, patient-specific cancer avatars. Focusing on colorectal cancer, we generated miniature tissues consisting of long-lived gut-shaped human colon epithelia (‘mini-colons’) that stably integrate cancer cells and their native tumor microenvironment in a format optimized for real-time, high-resolution evaluation of cellular dynamics. We demonstrate the potential of this system through several applications: a comprehensive evaluation of drug effectivity, toxicity and resistance in anticancer therapies; the discovery of a mechanism triggered by cancer-associated fibroblasts that drives cancer invasion; and the identification of immunomodulatory interactions among different components of the tumor microenvironment. Similar approaches should be feasible for diverse tumor types.

现有的类器官模型无法完全捕捉癌症的复杂性，因为它们缺乏足够的多细胞多样性、组织水平组织、生物耐久性和实验灵活性。因此，许多多因素癌症过程，特别是那些涉及肿瘤微环境的癌症过程，很难离体研究。为了克服这些限制，我们在此实施了组织工程和微加工技术来开发拓扑生物学复杂的、患者特异性的癌症化身。专注于结直肠癌，我们生成了由长寿的肠状人类结肠上皮（“迷你结肠”）组成的微型组织，这些组织以针对实时、高分辨率评估而优化的格式稳定地整合癌细胞及其天然肿瘤微环境细胞动力学。我们通过多种应用展示了该系统的潜力：抗癌治疗中药物有效性、毒性和耐药性的综合评估；发现由癌症相关成纤维细胞触发的驱动癌症侵袭的机制；以及肿瘤微环境不同成分之间免疫调节相互作用的鉴定。类似的方法对于不同的肿瘤类型应该是可行的。