Organoid Cultures Derived From Patients With Papillary Thyroid Cancer

Context: Papillary thyroid cancer (PTC) has been one of the most frequent endocrine malignancies around the world. Although most PTC patients have a favorable prognosis, a subgroup of patients die, especially when disease recurrence occurs.There is a pressing need for clinically relevant preclinical thyroid cancer models for personalized therapy because of the lack of in vitro models that faithfully represent the biology of the parental tumors.Objective: To understand thyroid cancer and translate this knowledge to clinical applications, patient-derived PTC organoids as a promising new preclinical model were established.Methods: Surgically resected PTC primary tissues were dissociated and processed for organoid derivation. Tumor organoids were subsequently subjected to histological characterization, DNA sequencing, drug screen, and cell proliferation assay, respectively.Results: We describe a 3-dimensional culture system for the long-term expansion of patient-derived PTC organoid lines. Notably, PTC organoids preserve the histopathological profiles and genomic heterogeneity of the originating tumors. Drug sensitivity assays of PTC organoids demonstrate patient-specific drug responses, and large correlations with the respective mutational profiles. Estradiol was shown to promote cell proliferation of PTC organoids in the presence of estrogen receptor alpha (ER alpha), regardless of the expression of ER beta and G protein-coupled ER.Conclusion: These data suggest that these newly developed PTC-derived organoids may be an excellent preclinical model for studying clinical response to anticancer drugs in a personalized way, as well as provide a potential strategy to develop prevention and treatment options for thyroid cancer with ER alpha-specific antagonists.