Tumor Microenvironment-on-a-Chip: Construction and Application in Traditional Chinese Medicine Anti-Tumor Therapy.

Cancer is the second leading cause of death worldwide, and tumor heterogeneity remains a major obstacle to effective therapy. In vitro reconstruction of the tumor microenvironment (TME) is particularly challenging because of its complexity, dynamic nature, and spatial heterogeneity, which limits the predictive value of conventional models for anticancer drug evaluation. Traditional Chinese medicine (TCM) has attracted increasing attention in cancer therapy owing to its multi-component, multi-target, and multi-pathway therapeutic characteristics. However, the complexity of TCM formulations and the diversity of their bioactive constituents make their pharmacological mechanisms difficult to elucidate using conventional experimental models. Microfluidic tumor microenvironment-on-a-chip (TME-on-a-chip) platforms integrate engineered cell culture with dynamic perfusion systems to recapitulate key structural, biochemical, and cellular features of the TME, thus providing a more physiologically relevant platform for anticancer research. With advantages such as low sample consumption, precise spatiotemporal control, multicellular co-culture, and real-time monitoring, these platforms provide a promising strategy for evaluating the efficacy and microenvironment-dependent effects of TCM-derived compounds and formulations. In this review, we summarize recent advances in the construction of TME-on-a-chip models, including multicellular organization, extracellular matrix simulation, vascularization, and immune microenvironment reconstruction, and discuss how these systems can be applied to key questions in TCM-based anticancer research. We further analyze current technical and methodological challenges that limit their broader adoption in TCM research and highlight future directions for promoting mechanism-driven and precision-oriented development of TCM in cancer therapy.