Abstract
Accumulated research has revealed the multifaceted roles of thyroid hormone receptors (TRs) as potent tumor suppressors across various cancer types. This review explores the intricate mechanisms underlying TR-mediated tumor suppression, drawing insights from preclinical mouse models and cancer biology. This review examines the tumor-suppressive functions of TRs, particularly TRβ, in various cancers using preclinical models, revealing their ability to inhibit tumor initiation, progression, and metastasis. Molecular mechanisms underlying TR-mediated tumor suppression are discussed, including interactions with oncogenic signaling pathways like PI3K-AKT, JAK-STAT, and transforming growth factor β. Additionally, this paper examines TRs' effect on cancer stem cell activity and differentiation, showcasing their modulation of key cellular processes associated with tumor progression and therapeutic resistance. Insights from preclinical studies underscore the therapeutic potential of targeting TRs to impede cancer stemness and promote cancer cell differentiation, paving the way for precision medicine in cancer treatment and emphasizing the potential of TR-targeted therapies as promising approaches for treating cancers and improving patient outcomes.