Spheroid‐on‐a‐Chip Platforms for Tumor Microenvironment and Drug Development

Abstract Despite significant advancements in oncology research and therapeutic interventions, cancer continues to be the leading cause of mortality worldwide. The key challenge in addressing this pressing issue lies in the lack of precision diagnosis and a limited understanding of the nature and how the tumor microenvironment responds to therapeutic interventions. Research focusing on understanding the impact of tumor microenvironment (TME) heterogeneity on the response to cancer drugs is crucial to ensure efficient therapy. Conventional models exhibit significant constraints, including the inability to accurately imitate tumors’ complex 3D architecture and dynamic microenvironment. Recent developments in Spheroid‐On‐a‐Chip (SoC) technology provide a significant alternative, offering a tumor microenvironment closer to that of human tissue. This review explores the recent developments in SoC modeling, highlighting key spheroid formation mechanisms and techniques. The applications of the SoC platform to mimic the essential features of the tumor microenvironment and their potential role in anticancer drug development are summarized. The advantages and challenges of the technologies behind SoC devices compared to traditional in vitro models are further discussed. Lastly, future directions for transforming cancer research and improving drug development are suggested.