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- Title
Organoid Cultures Derived From Patients With Papillary Thyroid Cancer.
- Authors
Dong Chen; Yawen Tan; Zhichao Li; Wujiao Li; Lei Yu; Wei Chen; Yuchen Liu; Lisa Liu; Liangfeng Guo; Weiren Huang; Yongsheng Zhao; Chen, Dong; Tan, Yawen; Li, Zhichao; Li, Wujiao; Yu, Lei; Chen, Wei; Liu, Yuchen; Liu, Lisa; Guo, Liangfeng
- Abstract
<bold>Context: </bold>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.<bold>Objective: </bold>To understand thyroid cancer and translate this knowledge to clinical applications, patient-derived PTC organoids as a promising new preclinical model were established.<bold>Methods: </bold>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.<bold>Results: </bold>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 α (ERα), regardless of the expression of ERβ and G protein-coupled ER.<bold>Conclusion: </bold>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 ERα-specific antagonists.
- Subjects
THYROID cancer; URIDINE; THYROTROPIN receptors; VASCULAR endothelial growth factor receptors; RESEARCH; CELL culture; CLINICAL drug trials; THYROID gland tumors; RESEARCH methodology; CELL physiology; ANTINEOPLASTIC agents; TISSUE culture; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; TISSUES; GENE expression profiling; PHARMACODYNAMICS
- Publication
Journal of Clinical Endocrinology & Metabolism, 2021, Vol 106, Issue 5, p1410
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgab020