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

Sep 23, 2026

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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, provide a framework for elucidating tumor biology and therapeutic resistance. This review summarizes advances in patient-derived and PSC-derived organoid systems, including tumor microenvironment modeling, progression analysis, drug screening, and patient-tailored strategies to bridge basic research and clinical translation.

LanguageEnglish

CategoryHealthcare

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Pages12

Reading Time30 min

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Abstract

Introduction

Molecular drivers and progression

Hallmark mutations in well-differentiated thyroid cancer

Transition to aggressive subtypes

European Thyroid Journal (2025) 14 e240392 [https://doi.org/10.1530/ETJ-24-0392](https://doi.org/10.1530/ETJ-24-0392) REVIEW Received 17 December 2024 Accepted 20 June 2025 Available online 20 June 2025 Version of Record published 2 July 2025 | NOVEL INSIGHTS IN ADVANCED THYROID CARCINOMA: FROM MECHANISMS TO TREATMENTS
Development of 3D organoid models to study aggressive thyroid cancers
Eduardo Rios-Morris*, Verla Ivan Tientcheu Ngafﬁ*, Sabine Costagliola and Mírian Romitti􀀁
Institut de Recherche Interdisciplinaire en Biologie Humaine et Molculaire (IRIBHM) Jacques E. Dumont, Universit Libre de Bruxelles (ULB), Brussels, Belgium
Correspondence should be addressed [to M Romitti:](to M Romitti: mirian.romitti@ulb.be)[ mirian.romitti@ulb.be](to M Romitti: mirian.romitti@ulb.be)[ ](to M Romitti: mirian.romitti@ulb.be)*(E Rios-Morris and V I Tientcheu Ngafﬁ contributed equally to this work)
This article forms part of a special collection titled ‘ Novel Insights in Advanced Thyroid Carcinoma: From Mechanisms to Treatments’. The editors of this collection are Dr Iñigo Landa (Group Leader, Institut Gustave Roussy in Villejuif, Grand Paris, France), Professor Iwao Sugitani (Graduate School Professor & Chairman, Department of Endocrine Surgery, Nippon Medical School, Tokyo, Japan) and Professor Eﬁsio Puxeddu (Associate Professor of Endocrinology, Department of Medicine and Surgery, University of Perugia, Italy) . | | --- | | Abstract
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 ofTC 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.
Keywords: thyroid cancer; organoids; in vitro models | Introduction Thyroid cancer (TC) is the most common endocrine malignancy, with increasing incidence over recent decades (1) . Follicular cell-derived neoplasms include well-differentiated, high-grade differentiated, and Published by Bioscientiﬁca Ltd. [https://etj.bioscienti](https://etj.bioscienti)ﬁ[ca.com](ca.com) © 2025 the author(s) poorly/undifferentiated thyroid carcinomas. Well-differentiated thyroid carcinoma (WDTC) comprises 90% of thyroid malignancies, including papillary thyroid carcinoma (PTC) (∼80% of cases), This work is licensed under a Creative Commons Attribution-NonCommercialNoDerivatives 4 .0 International License. E Rios-Morris et al. European Thyroid Journal (2025) 14 e240392 [https://doi.org/10.1530/ETJ-24-0392](https://doi.org/10.1530/ETJ-24-0392) follicular thyroid carcinoma

FAQs

Why are advanced forms of thyroid cancer clinically challenging?

Poorly differentiated and anaplastic thyroid carcinomas show aggressive behavior, rapid progression, and resistance to standard therapies, leading to poor outcomes despite treatment efforts.

How do organoid models help study advanced thyroid carcinoma?

Organoid systems derived from patient samples or pluripotent stem cells enable more accurate disease representation, support analysis of tumor microenvironment features, and help investigate mechanisms underlying therapeutic resistance.

What applications of patient-derived organoids are emphasized in the review?

The review highlights creating PDTOs and using them to replicate essential tumor microenvironment characteristics, analyze tumor progression, perform drug screenings, and support personalized therapeutic strategies.

Sep 23, 2026

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