NOVEL INSIGHTS IN ADVANCED THYROID CARCINOMA: FROM MECHANISMS TO TREATMENTS: Development of 3D organoid models to study aggressive thyroid cancers.

Thyroid cancer (TC), particularly aggressive forms such as poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma, presents considerable clinical challenges due to limited treatment options and suboptimal outcomes. Organoid models, derived from patient samples or pluripotent stem cells (PSCs), offer a robust framework for elucidating the biology of these malignancies. Recent advancements in patient-derived tumor organoid (PDTO) methodologies have facilitated more accurate representations of TCs, encompassing the heterogeneity of the disease and mechanisms of therapeutic resistance. PSC-derived models have further enabled the investigation of fundamental driving mechanisms behind thyroid carcinogenesis. This review highlights the progress made in the development of TC organoids, focusing on their utility in studying aggressive subtypes. We discuss innovative techniques for creating PDTOs and their applications in replicating essential features of the tumor microenvironment (TME), analyzing tumor progression, conducting drug screenings, and developing personalized therapeutic strategies tailored to individual patients. While PDTOs have become the predominant model for TC research, PSC-derived organoids provide insights into early carcinogenic events and mutation-specific processes that are often inaccessible in established tumors. Through these advancements, we emphasize the critical role of organoid models in bridging the divide between fundamental research and clinical application, offering a promising avenue for uncovering novel insights into TC biology and enhancing therapeutic strategies.