甲状腺激素受体β（TRβ）是多种实体肿瘤中公认的肿瘤抑制因子。通过重新表达模型，已经阐明了TRβ的分子信号传导在几种癌症类型中的作用。值得注意的是，选择性激活内源性TRβ对肿瘤进展的潜在影响仍然未被充分探究。我们使用细胞和体内实验评估TRβ激动剂索贝曲美（GC-1）对一种特别侵袭性和去分化的癌症——间变性甲状腺癌（ATC）的影响。在这里，我们报告GC-1减少了肿瘤表现，降低了癌干细胞样细胞数量，并使具有不同突变背景的ATC细胞系重新分化。值得注意的是，这种选择性TRβ激活增强了抑制侵袭性细胞表型和干细胞生长的治疗剂的效果。在异种移植实验中，GC-1单独抑制了肿瘤生长，并且与激酶抑制剂索拉非尼一样有效。这些结果表明，选择性激活TRβ不仅在新生中诱导了肿瘤抑制程序，而且增强了抗癌剂的效果，揭示了间变性甲状腺癌和其他侵袭性实体肿瘤的潜在新组合疗法。© 2023 作者。由牛津大学出版社代表内分泌学会出版。保留所有权利。如需权限，请发送电子邮件至：journals.permissions@oup.com。

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.© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.