Department of Clinical and Experimental Medicine, Endocrinology Unit, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Semin Cancer Biol. 2022 Feb;79:197-202. doi: 10.1016/j.semcancer.2020.12.008. Epub 2021 Jan 18.
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.
近年来，对恶性细胞信号转导通路中分子机制的认识不断增加，最近发现了几种酪氨酸激酶（TKs），主要是 TK 受体（TKR），它们在许多类型癌症的发病机制中起主要作用。这些受体在生理上参与细胞生长和血管生成，在恶性细胞中可能发生突变或过度表达，是抗癌治疗的靶点。事实上，已经确定了几种针对特定改变途径的治疗剂，如 RET、BRAF、RAS、EGFR 和 VEGFR。酪氨酸激酶抑制剂（TKIs）通过与 TK 结构域的 ATP 结合位点竞争来影响 TK 依赖性致癌途径，从而阻断酶的活性，从而抑制多种癌症的生长和扩散。尽管治疗作用可能非常有效，但由于这些分子的多靶点抑制机制，它们可能会产生涉及多个生物系统的不良反应。在使用 TKI 治疗期间，已报道了甲状腺功能减退和甲状腺功能亢进，以及对涉及甲状腺激素代谢的酶活性的影响。本文回顾和讨论了导致甲状腺功能障碍和 TKI 患者血清甲状腺功能试验变化的发病机制。
