Krashin Eilon, Piekiełko-Witkowska Agnieszka, Ellis Martin, Ashur-Fabian Osnat
Translational Hemato-Oncology Laboratory, Meir Medical Center, Kfar-Saba, Israel.
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Front Endocrinol (Lausanne). 2019 Feb 13;10:59. doi: 10.3389/fendo.2019.00059. eCollection 2019.
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. 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.
甲状腺激素在正常生长、发育和代谢中起主要作用。一个多世纪的研究支持了甲状腺激素与各种癌症类型病理生理学之间的关系。在动物模型中的研究以及实验表明，甲状腺激素T3和T4对癌症增殖、凋亡、侵袭和血管生成有影响。甲状腺激素通过几种非基因组途径介导其对癌细胞的作用，包括激活质膜受体整合素αvβ3。此外，癌症的发生和发展受到甲状腺激素局部生物利用度失调的影响。病例对照研究和基于人群的研究在甲状腺激素与癌症的关联方面提供了相互矛盾的结果。然而，大量证据表明，亚临床和临床甲状腺功能亢进会增加几种实体恶性肿瘤的风险，而甲状腺功能减退可能会降低癌症的侵袭性或延迟癌症的发生。癌症治疗或甲状腺激素补充继发的甲状腺激素轴失调影响癌症预后的研究提供了额外的支持。最近在各种癌症类型中的临床前和临床研究进一步表明，在化学降低甲状腺激素或抑制其与整合素受体结合后，有令人鼓舞的结果。这篇综述全面概述了迄今为止进行的临床前和临床研究。
