Wnt/β-catenin signaling is a therapeutic target in anaplastic thyroid carcinoma

Wnt/β-catenin signaling is a therapeutic target in anaplastic thyroid carcinoma

Background Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy that has consistently shown Wnt/β-catenin (canonical) signaling activation in various study populations. There are currently no targetable treatments for BRAF -wildtype ATC and a lack of effective treatment for BRAF V600...

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Published in:Endocrine Vol. 86; no. 1; pp. 114 - 118
Main Authors: Diaz, Diana, Bergdorf, Kensey, Loberg, Matthew A., Phifer, Courtney J., Xu, George J., Sheng, Quanhu, Chen, Sheau-Chiann, Byrant, Jamal M., Tigue, Megan L., Hartmann, Heather, Rohde, Sarah L., Netterville, James L., Baregamian, Naira, Goettel, Jeremy A., Ye, Fei, Lee, Ethan, Weiss, Vivian L.
Format: Journal Article
Language:English
Published: New York Springer US 2024
Springer Nature B.V
Subjects:
Brief Report
Diabetes
Endocrinology
Humanities and Social Sciences
Internal Medicine
Malignancy
Medicine
Medicine & Public Health
multidisciplinary
Organoids
Population studies
Science
Therapeutic targets
Thyroid cancer
Thyroid carcinoma
Wnt protein
Xenografts
β-Catenin
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Summary:Background Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy that has consistently shown Wnt/β-catenin (canonical) signaling activation in various study populations. There are currently no targetable treatments for BRAF -wildtype ATC and a lack of effective treatment for BRAF V600E ATC. Our aim is to identify whether Wnt inhibitors could be potential therapeutic agents for ATC patients with limited treatment options. Methods In this Institutional Review Board-approved study, we utilize a cohort of 32 ATCs and 20 non-neoplastic multinodular goiters (MNG). We also use 4 ATC spheroid cell lines (THJ-16T, THJ-21T, THJ-29T, and THJ-11T) and two primary patient-derived ATC organoid cultures (VWL-T5 and VWL-T60). Finally, we use a murine xenograft mouse model of ATC for in vivo treatment studies. Results Using a large patient cohort, we demonstrate that this near-universal Wnt signaling activation is associated with ligand expression- rather than being mutationally-driven. We show that pyrvinium pamoate, a potent Wnt inhibitor, exhibits in vitro efficacy against both ATC cell lines and primary patient-derived ATC organoids VWL-T5 ( p  < 0.05) and VWL-T60 ( p  < 0.01) Finally, using a murine xenograft model of ATC, we show that pyrvinium significantly delays the growth of ATC tumors in THJ-16T ( p  < 0.005) and THJ-21T ( p  < 0.001). Conclusions We tested Wnt inhibitor treatment, both in vitro and in vivo, as a potential novel therapy for this highly lethal disease. Future large-scale studies utilizing multiple Wnt inhibitors will lay the foundation for the development of these novel therapies for patients with ATC.
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ISSN:1559-0100
1355-008X
1559-0100
DOI:10.1007/s12020-024-03887-0