INTERNATIONAL CONGRESS OF
CancerGenetics
Patient-Derived Thyroid Cancer Organoids for Precision Medicine: Preclinical Applications and Emerging Clinical Potential
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Parastou Mirzaei,1 Peyman Keyhanvar,2 Parisa Gozali,3 Abolfazl Barzegari,4,*
1. Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2. Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
3. Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
4. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Introduction: Thyroid cancer is the most common endocrine malignancy, and although most patients have a favorable prognosis, recurrent and metastatic disease remains clinically challenging (Yang et al., 2023). Conventional 2D cell lines and animal models have limitations in reproducing the tissue architecture and heterogeneity of patient tumors, highlighting the need for clinically relevant preclinical models (Yang et al., 2023). Patient-derived thyroid cancer organoids (PDTCOs) have emerged as three-dimensional models that can preserve important characteristics of the original tumor and may provide a functional platform for drug screening and precision oncology (Gao et al., 2026).
- Methods: Relevant studies published in English between 2020 and 2026 were retrieved from the PubMed and Google Scholar databases using combinations of the keywords “thyroid cancer,” “patient-derived organoid,” “thyroid organoid,” “drug screening,” and “precision medicine.” Relevant original research studies were prioritized, and six key studies were ultimately included. Recent reviews were additionally examined to identify research gaps and contextualize emerging applications.
- Results: Patient-derived papillary thyroid cancer (PTC) organoids can be expanded long-term while preserving parental tumor characteristics and patient-specific drug responses, supporting personalized drug screening (Chen et al., 2021). They also recapitulated radioactive iodine (RAI)-refractory phenotypes, suggesting potential for identifying I131-resistant patients (Sondorp et al., 2020). Beyond PTC, medullary thyroid carcinoma organoids retained tumor-specific molecular and functional features and showed potential for evaluating tyrosine kinase inhibitors (TKIs) and positron emission tomography (PET) tracers (Jager et al., 2025). In anaplastic thyroid cancer, organoid-based screening identified homoharringtonine as a potential therapeutic agent through PI3K–AKT–mTOR/TFEB-associated lysosomal dysfunction (Zhang et al., 2025). Clinically, a phase II study of 75 patients with locally advanced thyroid cancer found a 32.7% objective response rate among 55 patients receiving organoid-guided treatment, supporting the feasibility of individualized therapy (Guo et al., 2025). A microfluidic 3D-bioprinting platform generated patient-derived organoids within 10 days with a 76% success rate and 92% driver-gene concordance with parental tumors. These models recapitulated tumor heterogeneity, immune features, drug responses, and metastatic behavior, while NF-κB signaling was identified as a key regulator of organoid maturation and therapeutic response, potentially linking inflammatory and survival-related signaling to the acquisition of mature tumor-like characteristics and differential drug sensitivity (Gao et al., 2026). However, despite these promising preclinical findings and emerging clinical evidence, broader clinical translation remains limited. Future research should prioritize large, prospective multicenter studies to validate organoid-guided treatment strategies and assess their clinical utility.
- Conclusion: PDTCOs offer a promising platform for precision oncology by preserving tumor heterogeneity and predicting patient-specific drug responses. Integration with advanced technologies and prospective clinical validation may enable their translation into routine personalized therapy.
- Keywords: Thyroid cancer; Organoids; Precision Medicine; Drug Screening; Tumor Heterogeneity
