1. Academic Validation
  2. TRβ Agonism Induces Tumor Suppression and Enhances Drug Efficacy in Anaplastic Thyroid Cancer in Female Mice

TRβ Agonism Induces Tumor Suppression and Enhances Drug Efficacy in Anaplastic Thyroid Cancer in Female Mice

  • Endocrinology. 2023 Sep 13;bqad135. doi: 10.1210/endocr/bqad135.
Noelle E Gillis 1 2 Lauren M Cozzens 1 Emily R Wilson 1 Noah M Smith 1 Jennifer A Tomczak 1 Eric L Bolf 1 2 Frances E Carr 1 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, Vermont.
  • 2 University of Vermont Cancer Center, University of Vermont, Burlington, Vermont.
Abstract

Thyroid Hormone Receptor beta (TRβ) is a recognized tumor suppressor in numerous solid cancers. The molecular signaling of TRβ has been elucidated in several Cancer types through re-expression models. Remarkably, the potential impact of selective activation of endogenous TRβ on tumor progression remains largely unexplored. We used cell-based and in vivo assays to evaluate the effects of the TRβ agonist Sobetirome (GC-1) on a particularly aggressive and dedifferentiated Cancer, anaplastic thyroid Cancer (ATC). Here we report that GC-1 reduced the tumorigenic phenotype, decreased Cancer stem-like cell populations, and induced re-differentiation of the ATC cell lines with different mutational backgrounds. Of note, this selective activation of TRβ amplified the effects of therapeutic agents in blunting the aggressive cell phenotype and stem-cell growth. In xenograft assays, GC-1 alone inhibited tumor growth and was as effective as the kinase inhibitor, Sorafenib. These results indicate that selective activation of TRβ not only induces a tumor suppression program de novo but enhances the effectiveness of anti-cancer agents revealing potential novel combination therapies for ATC and other aggressive solid tumors.

Keywords

GC-1; Sobetirome; anaplastic thyroid cancer; thyroid hormone receptor.

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