The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

Abstract

Exemplifying the long-pursued thyroid hormones (TH)–cancer association, the TH–lung cancer association is a compelling, yet elusive, issue. The present narrative review provides background knowledge on the molecular aspects of TH actions, with focus on the contribution of TH to hallmarks of cancer. Then, it provides a comprehensive overview of data pertinent to the TH–lung cancer association garnered over the last three decades and identifies obstacles that need to be overcome to enable harnessing this association in the clinical setting. TH contribute to all hallmarks of cancer through integration of diverse actions, currently classified according to molecular background. Despite the increasingly recognized implication of TH in lung cancer, three pending queries need to be resolved to empower a tailored approach: (1) How to stratify patients with TH-sensitive lung tumors? (2) How is determined whether TH promote or inhibit lung cancer progression? (3) How to mimic the antitumor and/or abrogate the tumor-promoting TH actions in lung cancer? To address these queries, research should prioritize the elucidation of the crosstalk between TH signaling and oncogenic signaling implicated in lung cancer initiation and progression, and the development of efficient, safe, and feasible strategies leveraging this crosstalk in therapeutics.

Application of two-dimensional difference gel electrophoresis to identify protein changes between center, margin, and adjacent non-tumor tissues obtained from non-small-cell lung cancer with adenocarcinoma or squamous cell carcinoma subtype

“…For ADC L-triiodothyronine has been identified as negative upstream regulator. It is well known that thyroid hormone signaling is interrelated with lung cancer in a dual manner, either promoting or inhibitory [ 141 ] and our results suggest the latter is true for center of the tumor as compared to the margin. Identification of insulin as upstream regulator in SCC points out well described relationship between diabetes mellitus and cancers, including lung cancer, and hyperinsulinemia and exogenous insulin and insulin analog therapy were indicated as common risk factors for development of cancer [ 142 ].…”

Alterations of DNA methylation and expression of genes related to thyroid hormone metabolism in colon epithelium of obese patients

“…According to several lines of evidence, pro-cancerous effects of THs are exerted via either TRα or integrin avβ3 by promoting angiogenesis, proliferation, apoptosis suppression, evasion from immune surveillance, and metabolic reprogramming [ 9 ]. Convincing evidence suggests that TRβ is a tumor suppressor in several types of cancer, including thyroid, breast, colorectal and other solid tumors [ 10 ].…”

Influence of Transplantable Guerin’s Carcinoma in Rats on Activity of Hypothalamic-Pituitary-Thyroid and Hypothalamic-Pituitary-Adrenal Regulatory Axes of the Body

“…Исторически гипоталамо-гипофизарно-тиреоидная ось (ГГТ) и гипоталамогипофизарно-надпочечниковая ось (ГГН) рассматривались как настройщики циркулирующих уровней тиреоидных гормонов (ТГ) и глюкокортикоидов посредством механизмов отрицательной обратной связи [4]. Однако сейчас ГГТ и ГГН рассматриваются как динамическая система с пластичностью, позволяющая адаптироваться к сложным ситуациям и реагировать на стресс за счет регулирования «жизненных компромиссов между репродукцией, ростом, иммунитетом и базовым уровнем метаболизма» в условиях эволюционной экологии [5].…”