Tumor Organoid and Microenvironment Cocultures: Implications for Basic and Translational Cancer Research

Organoids are innovative three-dimensional (3D) cellular constructs, offering a unique platform to replicate the architectural and functional complexity of organs and tissues. In oncology, the tumor microenvironment (TME) dictates tumor evolution and therapeutic resistance. Consequently, therapies targeting TME components have emerged as a burgeoning frontier in cancer treatment. However, accurately recapitulating the dynamic, multicellular crosstalk of TME remains a significant hurdle for clinical translation. This review encapsulates the spectrum of current organoid coculture methodologies, ranging from direct coculture and air-liquid interface to advanced microfluidics and 3D bioprinting. These models not only deepen our understanding of the fundamental mechanisms at play in cancer but also evaluate emerging therapeutic modalities, such as antibody-drug conjugates and immunotherapy. By closely mimicking the in vivo tumor milieu, organoid cocultures enhance our ability to predict therapeutic outcomes and pave the way for the development of precision medicine approaches, thereby propelling forward the frontiers of oncology. This review aims to provide a comprehensive overview of organoid coculture models, spanning from construction methodologies to clinical applications. We envision this work serving as a definitive guide for the field, ultimately accelerating the transition from theoretical research to clinical practice.