One of the hurdles to the development of new anticancer therapies is the lack of in vitro models which faithfully reproduce the in vivo tumor microenvironment (TME). Understanding the dynamic relationships between the components of the TME in a controllable, scalable, and reliable setting would indeed support the discovery of biological targets impacting cancer diagnosis and therapy.

Cancer research is increasingly shifting from traditional two-dimensional (2D) cell culture toward three-dimensional (3D) culture models, which have been demonstrated to increase the significance and predictive value of in vitro data. In this scenario, microphysiological systems (also known as organs-on-chip) have emerged as a relevant technological platform enabling more predictive investigation of cell-cell and cell-ECM interplay in cancer, attracting a significant research effort in the last years.

This review illustrates one decade of progress in the field of tumor-microenvironment-on-chip (TMOC) approaches, exploiting either cell-laden microfluidic chambers or microfluidic confined tumor spheroids to model the TME. TMOCs have been designed to recapitulate several aspects of the TME, including tumor cells, the tumor-associated stroma, the immune system, and the vascular component. Significantly, the last aspect has emerged for its pivotal role in orchestrating cellular interactions and modulating drug pharmacokinetics on-chip. A further advancement has been represented by integration of TMOCs into multi-organ microphysiological systems, with the final aim to follow the metastatic cascade to target organs and to study the effects of chemotherapies at a systemic level.

We highlight that the increased degree of complexity achieved by the most advanced TMOC models has enabled scientists to shed new light on the role of microenvironmental factors in tumor progression, metastatic cascade, and response to drugs.

开发新抗癌疗法的障碍之一是缺乏忠实再现体内肿瘤微环境（TME）的体外模型。在可控、可扩展和可靠的环境中了解 TME 组件之间的动态关系确实有助于发现影响癌症诊断和治疗的生物靶标。

癌症研究越来越多地从传统的二维 (2D) 细胞培养转向三维 (3D) 培养模型，这已被证明可以提高体外数据的重要性和预测价值。在这种情况下，微生理系统（也称为芯片器官）已经成为一个相关的技术平台，能够对癌症中的细胞-细胞和细胞-ECM相互作用进行更具预测性的研究，在过去几年吸引了大量的研究工作。

这篇综述阐述了肿瘤微环境芯片 (TMOC) 方法领域十年来的进展，利用充满细胞的微流体室或微流体限制肿瘤球体来模拟 TME。 TMOC 旨在概括 TME 的多个方面，包括肿瘤细胞、肿瘤相关基质、免疫系统和血管成分。值得注意的是，最后一个方面因其在协调细胞相互作用和调节芯片上药物药代动力学方面的关键作用而出现。进一步的进展是将TMOC整合到多器官微生理系统中，最终目标是追踪靶器官的转移级联反应并在系统水平上研究化疗的效果。

我们强调，最先进的 TMOC 模型的复杂性不断提高，使科学家能够对微环境因素在肿瘤进展、转移级联和药物反应中的作用提供新的认识。