tumor microenvironment

Cancer is a highly heterogeneous and dynamic disease whose progression, metastasis, therapeutic resistance, and immune escape are strongly regulated by the tumor microenvironment (TME). However, conventional two-dimensional (2D) cell culture systems and animal models often fail to recapitulate the structural organization, multicellular interactions, biochemical gradients, and mechanical properties of native tumors, thereby limiting the translational efficiency of preclinical cancer research and drug development. In recent years, in vitro three-dimensional (3D) biomimetic tumor models-including tumor spheroids, tumor organoids, and tumor-on-a-chip systems—have emerged as powerful platforms for reconstructing physiologically relevant tumor microenvironments and investigating complex tumor behaviors.In this review, we systematically summarize the construction principles, biological characteristics, advantages, and limitations of major 3D biomimetic tumor models. We further discuss their recent applications in drug screening, precision medicine, tumor heterogeneity research, cancer stem cell investigation, metastasis, therapeutic resistance, and immunotherapy evaluation. Particular emphasis is placed on the comparative advantages of different 3D systems in modeling dynamic tumor–microenvironment interactions and supporting translational oncology research. Additionally, we will discuss the current problems of vascularisation, extracellular matrix biomimetics, experimental reproducibility, standardisation, and large-scale clinical translation. Finally, we present some new directions for future work, including three-dimensional bioprinting, multi-omics technology, artificial intelligence, and multi-organ-on-a-chip platforms, which may further improve the physiological relevance and predictive power of next-generation tumor models.In short, this review has listed the current progress of 3D biomimetic tumour modelling and discussed some prospects for its use in mechanistic studies of cancer, drug discovery, etc.