Tumor spheroids versus organoids: defining the more suitable three-dimensional model for cancer research.

INTRODUCTION: Three-dimensional cell culture systems, such as spheroids and organoids, have emerged as tools for modeling biological processes beyond conventional two-dimensional cultures. Spheroids, formed by self-aggregation of cell lines or primary cells, are simple multicellular structures ideal for drug screening due to their reproducibility and compatibility with high-throughput platforms. Organoids, typically derived from stem cells or patient tissues, develop structures that mimic tissue architecture and genetic features, including tumor heterogeneity. AREAS COVERED: This review examines the fundamental differences between spheroid and organoid models, focusing on their cellular origin, structural features, methods of generation, and applications in tumor research. The authors discuss the advantages and limitations of each system and highlight how experimental goals, scalability requirements, and biological complexity influence model selection. This review is based on structured literature searches of PubMed/MEDLINE, Web of Science, and Google Scholar for articles published between January 1988 and July 2026. EXPERT OPINION: Tumor spheroid models offer practical and scalable solutions to screening and mechanistic studies, while organoids offer biological complexity and better representation of patient-derived disease characteristics. These models improve the physiological relevance of in-vitro studies, help bridge the gap between simplified cell culture systems and in-vivo testing, and reduce dependence on animal model testing.