AI Article Synopsis

  • Anaplastic thyroid carcinoma (ATC) is a highly aggressive cancer with no effective treatments for certain genetic types, prompting the exploration of Wnt inhibitors as potential therapies.
  • The study involved a cohort of ATC patients and various cell lines to investigate the efficacy of pyrvinium pamoate, a Wnt inhibitor, showing promising results in both lab tests and mouse models.
  • Results indicated that Wnt signaling activation in ATC is primarily due to ligand expression and not mutations, suggesting that further research on Wnt inhibitors could lead to new treatment options for ATC patients.

Article Abstract

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 BRAFATC. 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444896PMC
http://dx.doi.org/10.1007/s12020-024-03887-0DOI Listing

Publication Analysis

Top Keywords

anaplastic thyroid
8
thyroid carcinoma
8
atc
8
signaling activation
8
cell lines
8
primary patient-derived
8
patient-derived atc
8
wnt/β-catenin signaling
4
signaling therapeutic
4
therapeutic target
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!