Effects of tyrosine kinase inhibitors on thyroid function and thyroid hormone metabolism

Semin Cancer Biol. 2022 Feb;79:197-202. doi: 10.1016/j.semcancer.2020.12.008. Epub 2021 Jan 18.

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.

Keywords: Deiodinases; Hypothyroidism; Thyroid dysfunction; Thyroid hormone metabolism; Thyrotoxicosis; Tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Humans
  • Hypothyroidism / chemically induced
  • Hypothyroidism / pathology*
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Thyroid Function Tests
  • Thyroid Gland / pathology
  • Thyroid Hormones / metabolism
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Thyrotoxicosis / chemically induced
  • Thyrotoxicosis / pathology*

Substances

  • Protein Kinase Inhibitors
  • Thyroid Hormones
  • Receptor Protein-Tyrosine Kinases