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

Abstract

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 (I131), resulting in total thyroid ablation. Unfortunately, about 15-33% of PTC patients are unable to take up I131, 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 I131-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 I131-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 I131-resistant patients, in order to reduce RAI overtreatment and its many side effects for thyroid cancer patients.

Biomaterial-based platforms for cancer stem cell enrichment and study

“…Organoids, a novel stem cell study model, have been introduced in the study of CSCs through the embedding of CSCs and other cancer-related cells in Matrigel or ECM-like biomaterials 6 . This model not only supports the CSC enrichment but also recapitulates the histopathology and cellular heterogeneity of tumors [7][8][9][10] . Additionally, unlike conventional study systems based on cancer cell lines, organoids can be generated from specimens of individual patients, thereby enabling the development of personalized therapeutic regimens 6 .…”

Research Progress, Challenges, and Breakthroughs of Organoids as Disease Models

“…We have performed much in-depth investigation on the origin, pathology, and genetics of cancer in the past few decades, and we found that the knowledge gained from cell lines and PDX is not entirely consistent with the actual clinical situation. We are increasingly aware that cancer has different heterogeneity and , 2015), lung cancer (Dijkstra et al, 2020), liver cancer (Nuciforo et al, 2018), prostate cancer (Puca et al, 2018), breast cancer (Han et al, 2020), gastric cancer (Yan et al, 2018), pancreatic cancer (Seino et al, 2018), lymphatic cancer (Tian et al, 2015), esophageal cancer (Li et al, 2018), thyroid cancer (Sondorp et al, 2020), among others (Figure 2). These studies have shown that tumor organoids are highly similar to the original tumors in terms of genetic specificity, epigenetic characteristics, morphology, metabolism, proliferation rate, and metastatic potential.…”

“…The recently developed 3D culture technology has led to the development of new and more physiological organoids, thus creating new and more targeted therapies. In the more than 10 years since the emergence of organoids, scientists successfully cultivated all kinds of tumor organoids, such as bladder cancer ( Lee et al, 2018b ), colorectal cancer ( van de Wetering et al, 2015 ), lung cancer ( Dijkstra et al, 2020 ), liver cancer ( Nuciforo et al, 2018 ), prostate cancer ( Puca et al, 2018 ), breast cancer ( Han et al, 2020 ), gastric cancer ( Yan et al, 2018 ), pancreatic cancer ( Seino et al, 2018 ), lymphatic cancer ( Tian et al, 2015 ), esophageal cancer ( Li et al, 2018 ), thyroid cancer ( Sondorp et al, 2020 ), among others ( Figure 2 ). These studies have shown that tumor organoids are highly similar to the original tumors in terms of genetic specificity, epigenetic characteristics, morphology, metabolism, proliferation rate, and metastatic potential.…”

Efficacy of a Graphene Oxide/Chitosan Sponge for Removal of Radioactive Iodine-131 from Aqueous Solutions

“…Recent research by Zupunski et al [ 3 ] found a correlation between subjects exposed to iodine-131 from Chernobyl’s fallout during childhood at age ≤18 years and thyroid cancer risk. This is of great concern, as iodine-131 is routinely administered as a radiopharmaceutical in nuclear medicine in the form of sodium iodide (NaI) for diagnosis and treatment of thyroid disease [ 4 ]. Approximately 80% of the administered iodine-131 is excreted in the urine [ 5 ]; therefore, it has potential to be discharged to sewage wastewater if not carefully controlled.…”