The Application of 3D Cell Culture in Thyroid Cancer.

Abstract

Thyroid cancer is the most prevalent endocrine malignancy and displays pronounced heterogeneity in histology, molecular alterations, and therapeutic responses, particularly in poorly differentiated, anaplastic, and radioiodine-refractory disease. Conventional two-dimensional cultures and animal models inadequately recapitulate the three-dimensional (3D) architecture, tumor microenvironment, and thyroid-specific functions, limiting their translational relevance. Recent advances in 3D culture technologies, especially organoid models, have provided physiologically relevant platforms for in vitro thyroid cancer research. This review summarizes current strategies for constructing thyroid cancer 3D models, with emphasis on spheroid and organoid systems, encompassing scaffold-free, scaffold-based cultures, and emerging bioengineering platforms such as dynamic bioreactors, decellularized extracellular matrices, microfluidic organ-on-a-chip systems, and 3D bioprinting. We further highlight key applications of thyroid cancer organoids in disease modeling, drug screening, radioiodine response prediction, and personalized therapeutic evaluation and discuss remaining challenges and future directions toward improved standardization and clinical translation. Compared with previous reviews on thyroid 3D culture, this work provides a more integrated and updated perspective by systematically linking culture strategies with tumor microenvironmental complexity, functional thyroid phenotypes, and emerging translational platforms, thereby offering a comprehensive framework for next-generation thyroid cancer modeling.