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Patient-Derived Papillary Thyroid Cancer Organoids for Radioactive Iodine Refractory Screening

Sondorp, L. H. J., Ogundipe, V. M. L., Groen, A. H., Kelder, W., Kemper, A., Links, T. P., Coppes, R. P. & Kruijff, S., Nov-2020, In : Cancers. 12, 11, p. 1-15 15 p., 3212.

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Simple Summary

Over the past three decades, the incidence of thyroid cancer has been rising, with 90% being the well-differentiated thyroid cancer subtype. After diagnosis and surgical removal of the thyroid gland, radioactive iodine is administered to induce a localized post-operative radiation treatment. However, in 15-33% of papillary thyroid cancer cases, the cells are unable to take up radioactive iodine, resulting in an ineffective treatment which sometimes has severe side effects. Pre-treatment diagnosis of non-responding patients would prevent ineffective and toxic iodine treatment. Therefore, in this study, we developed a patient-derived papillary thyroid cancer organoid model. Patient-derived organoids responding or not responding to radioactive iodine clearly resembled the tumor of origin, but showed clear differences in sodium/iodide symporter expression. Our results indicate that thyroid cancer organoids might be a suitable tool for the early diagnosis of non-responding patients, in order to eventually reduce radioactive iodine overtreatment and its many side effects for thyroid cancer patients.

Patients with well-differentiated thyroid cancer, especially papillary thyroid cancer (PTC), are treated with surgical resection of the thyroid gland. This is followed by post-operative radioactive iodine (I-131), resulting in total thyroid ablation. Unfortunately, about 15-33% of PTC patients are unable to take up I-131, limiting further treatment options. The aim of our study was to develop a cancer organoid model with the potential for pre-treatment diagnosis of these I-131-resistant patients. PTC tissue from thirteen patients was used to establish a long-term organoid model. These organoids showed a self-renewal potential for at least five passages, suggesting the presence of cancer stem cells. We demonstrated that thyroid specific markers, a PTC marker, and transporters/receptors necessary for iodine uptake and thyroid hormone production were expressed on a gene and protein level. Additionally, we cultured organoids from I-131-resistant PTC material from three patients. When comparing PTC organoids to radioactive iodine (RAI)-refractory disease (RAIRD) organoids, a substantial discordance on both a protein and gene expression level was observed, indicating a treatment prediction potential. We showed that patient-derived PTC organoids recapitulate PTC tissue and a RAIRD phenotype. Patient-specific PTC organoids may enable the early identification of I-131-resistant patients, in order to reduce RAI overtreatment and its many side effects for thyroid cancer patients.

Original languageEnglish
Article number3212
Pages (from-to)1-15
Number of pages15
JournalCancers
Volume12
Issue number11
Publication statusPublished - Nov-2020

    Keywords

  • patient-derived tumor organoids, three-dimensional culture, tumor organoids, papillary thyroid carcinoma, cancer stem cells, treatment prediction, RAI therapy, RADIOIODINE THERAPY, STEM-CELLS, ZO-1, LIVER, MODEL, LOCALIZATION, EXPRESSION, MORTALITY, CARCINOMA, EXPANSION

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