Abstract
Thyroid hormones take major part in normal growth, development and metabolism. Over a century of research has supported a relationship between thyroid hormones and the pathophysiology of various cancer types. In vitro studies as well as research in animal models demonstrated an effect of the thyroid hormones T3 and T4 on cancer proliferation, apoptosis, invasiveness and angiogenesis. Thyroid hormones mediate their effects on the cancer cell through several non-genomic pathways including activation of the plasma membrane receptor integrin αvβ3. Furthermore, cancer development and progression are affected by dysregulation of local bioavailability of thyroid hormones. Case-control and population-based studies provide conflicting results regarding the association between thyroid hormones and cancer. However, a large body of evidence suggests that subclinical and clinical hyperthyroidism increase the risk of several solid malignancies while hypothyroidism may reduce aggressiveness or delay the onset of cancer. Additional support is provided from studies in which dysregulation of the thyroid hormone axis secondary to cancer treatment or thyroid hormone supplementation was shown to affect cancer outcomes. Recent preclinical and clinical studies in various cancer types have further shown promising outcomes following chemical reduction of thyroid hormones or inhibition or their binding to the integrin receptor. This review provides a comprehensive overview of the preclinical and clinical research conducted so far.
Highlights
Thyroid hormones (TH) are key regulators of essential cellular processes including proliferation, differentiation, apoptosis, and metabolism
While these findings suggest that hypothyroidism slows breast cancer progression, the study was limited by its retrospective nature and by the fact that the diagnosis of hypothyroidism was based on information from medical charts rather than hormone values
We aimed in this review to shed light on this association in order to clarify which types of cancer are thyroid-hormone sensitive and are expected to favorably respond to manipulation of the thyroid hormone axis
Summary
Thyroid hormones (TH) are key regulators of essential cellular processes including proliferation, differentiation, apoptosis, and metabolism. Hypothalamic thyrotropin-releasing hormone (TRH), activates the pituitary gland to synthesize and secret thyroid stimulating hormone (TSH), which in turn acts at the thyroid gland to stimulate TH synthesis and secretion [1]. Tetraiodothyronine (T4), the main hormone synthesized in the thyroid gland, is catalyzed to the Triiodothyronine (T3) by specific iodothyronine deiodinases [2]. T3 acts as the principal TH mediating metabolic activity, via formation of complexes between T3 and nuclear thyroid hormone receptors alpha (TRα) and beta (TRβ). This nuclear T3-receptor complex binds to thyroid hormone response elements on specific genes, regulating their transcription [3]. Diseases associated with excess of TH (hyperthyroidism) and lack of TH (hypothyroidism) are common and present with distinct clinical symptoms
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
