Effects of tyrosine kinase inhibitors on thyroid function and thyroid hormone metabolism. (February 2022)

• Record Type: Journal Article
• Authors: Basolo, Alessio; Matrone, Antonio; Elisei, Rossella; Santini, Ferruccio
• Is Part Of: Seminars in cancer biology. Volume 79(2022)
• Page Start: 197
• Page End: 202
• Publication Date: 2022-02
• Subjects: TK tyrosine kinase -- TKR tyrosine kinase receptor -- TKI tyrosine kinase inhibitors -- VEGFR vascular endothelial growth factor receptor -- PDGFR platelet-derived growth factor receptor -- EGFR epidermal growth factor receptor -- RET rearranged during transfection -- MET hepatocyte growth factor receptor -- FGFR fibroblast growth factor receptor -- T2 3, 3′-diiodothyronine -- T3 3, 5, 3'-triiodothyronine -- T4 3, 5, 3', 5'-tetraiodothyronine -- rT3 3, 3', 5'-triiodothyronine; Thyroid dysfunction -- Tyrosine kinase inhibitors -- Thyroid hormone metabolism -- Deiodinases -- Thyrotoxicosis -- Hypothyroidism; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2020.12.008
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: The increasing knowledge of the molecular mechanisms in the cell signaling pathways of malignant cells, has recently led to the discovery of several tyrosine kinases (TKs), mainly TK receptors (TKR), which play a major role in the pathogenesis of many types of cancer. These receptors, physiologically involved in cell growth and angiogenesis, may harbor mutations or be overexpressed in malignant cells, and represent a target for anticancer therapy. Indeed, several therapeutic agents targeting specific altered pathways such as RET, BRAF, RAS, EGFR and VEGFR, have been identified. Tyrosine kinase inhibitors (TKIs) affect TK dependent oncogenic pathways by competing with ATP binding sites of the TK domain, thus blocking the activity of the enzyme, and thereby inhibiting the growth and spread of several cancers. Although the therapeutic action may be very effective, these molecules, due to their mechanism of multitargeted inhibition, may produce adverse events involving several biological systems. Both hypothyroidism and thyrotoxicosis have been reported during treatment with TKI, as well as an effect on the activity of enzymes involved in thyroid hormone metabolism. The pathogenic mechanisms leading to thyroid dysfunction and changes in serum thyroid function tests occurring in patients on TKI are reviewed and discussed in this manuscript.