Spatial heterogeneity in anaplastic thyroid carcinoma: Mechanistic insights and clinical translation through single-cell and spatial transcriptomics

Anaplastic thyroid carcinoma (ATC) is a highly lethal malignancy whose therapeutic resistance is driven by profound intra-tumor heterogeneity and a complex tumor microenvironment. This review synthesizes how single-cell and spatial transcriptomic technologies are transforming our understanding of ATC by systematically decoding its cellular composition and spatial architecture. These approaches have uncovered novel aggressive cell states, delineated immunosuppressive functional niches, and elucidated the critical cell-cell communication networks that underlie treatment failure. Consequently, the therapeutic paradigm for ATC is shifting from targeting isolated driver mutations towards strategically remodeling the entire tumor ecosystem. The integration of these high-resolution insights is paving the way for the development of novel precision medicine strategies aimed at overcoming resistance in this formidable disease.