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Novel anaplastic thyroid cancer PDXs and cell lines: Expanding preclinical models of genetic diversity

Journal of Clinical Endocrinology and Metabolism Jun 25, 2021

Maniakas A, Henderson YC, Hei H, et al. - In view of the necessity for robust preclinical thyroid cancer models to adequately develop and study novel therapeutic agents for anaplastic thyroid cancer (ATC), a rare, aggressive, and deadly disease, researchers herein developed distinct ATC patient-derived xenograft (PDX) models concurrently with cell lines and characterized them in vitro and in vivo. They surgically obtained fresh thyroid tumor from patients with a preoperative diagnosis of ATC and divided them for concurrent cell line and PDX model development. Generating single cells through enzymatic digestion, they created cell lines. Development of PDX models was done after direct subcutaneous implantation of fresh tumor on the flank of immune compromised/athymic mice. Overall, they performed development of six ATC PDX models and four cell lines with distinct genetic profiles, which makes them excellent tools for preclinical therapeutic trials. One BRAF/TP53/CDKN2A, one BRAF/CDKN2A, one BRAF/TP53, one TP53 only, one TERT-promoter/HRAS, and one TERT-promoter/KRAS/TP53/NF2/NFE2L2 mutated phenotype were identified in mutational characterization.

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