Engineering Heterogeneous Tumor Models for Biomedical Applications

Tumor tissue engineering holds great promise for replicating the physiological and behavioral characteristics of tumors in vitro. Advances in this field have led to new opportunities for studying the tumor microenvironment and exploring potential anti-cancer therapeutics. However, the main obstacle to the widespread adoption of tumor models is the poor understanding and insufficient reconstruction of tumor heterogeneity. In this review, the current progress of engineering heterogeneous tumor models is discussed. First, the major components of tumor heterogeneity are summarized, which encompasses various signaling pathways, cell proliferations, and spatial configurations. Then, contemporary approaches are elucidated in tumor engineering that are guided by fundamental principles of tumor biology, and the potential of a bottom-up approach in tumor engineering is highlighted. Additionally, the characterization approaches and biomedical applications of tumor models are discussed, emphasizing the significant role of engineered tumor models in scientific research and clinical trials. Lastly, the challenges of heterogeneous tumor models in promoting oncology research and tumor therapy are described and key directions for future research are provided. This review focuses on the underlying fundamentals and applications of heterogeneous tumor engineering. It concludes the causes of tumor heterogeneity, including signal pathways, cell proliferation, and structures. It also discusses the potentials and advances of bottom-up complex tumor engineering. Finally, it provides insights into the biomedical applications of heterogeneous tumor models, highlighting current challenges and outlining future directions.image