Department of Medical Oncology Laboratory, All India Institute of Medical Sciences, New Delhi, India.
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Asian Pac J Cancer Prev. 2023 Feb 1;24(2):375-387. doi: 10.31557/APJCP.2023.24.2.375.
Thyroid cancer's incidence has increased by leaps and bounds over the last years and accounts for 2.8% of new cases of cancers. This increasing bar is partially assisted by enormous screening to understand the sub-clinical status. Advanced tumor growth is the leading cause of thyroid cancer-associated death. However, the complete understanding of the underlying cause is still to be disclosed. The updated clinical assessment evidenced a few major oncogenes viz. RAS, BRAF, and RET as key drivers in the development and progression of thyroid cancer. The BRAF mutation, a major cause of aggressive tumor type in papillary thyroid carcinoma, is frequently reported. The characteristic oncogenic changes imply thyroid cancer to be clinically an ideal model for targeted therapy against RET, RAS, and BRAF mutation. Though the sensitive biochemical marker assay has been improvised, the diagnosis of thyroid follicular neoplasms is still a big challenge as the biopsy aspiration cannot define the nature of the tumor in 30% of the cases. The main hurdle is assisted distinction between follicular thyroid lesions. The discrimination between follicular thyroid adenomas and carcinomas is histologically accomplished. This strictly necessitates the identification of sensitive diagnostic/prognostic markers to mitigate the risk of thyroid cancer and to avoid the unnecessary hurdles of biopsy and surgery. An array of prognostic biomarkers is being used for the diagnosis of thyroid cancer. However, Estrogen Related Receptor Gamma (ERRγ) is setting a new benchmark among the clinical biomarkers. The dramatic expression of ERRγ in thyroid cancer enables itself not only to serve as a characteristic diagnostic marker but also as a therapeutic target. Recently, we have reported that ERRγ is upregulated in 96 papillary thyroid cancer (PTC) and 26 poorly differentiated/ anaplastic thyroid cancer (ATC) samples. Various synthetic ERRγ inverse agonists viz. GSK5182, DN200434, and 24e are fully proved to modulate ERRγ expression in ATC to attain partial cure. If this finding can be assayed on a larger scale the evaluation of this marker may be warranted and informative. This review article highlights the ascending sheds of clinical biomarkers of thyroid cancer. This also reveals the clinical importance of ERRγ as an evolving diagnostic and therapeutic target in thyroid cancer.
近年来，甲状腺癌的发病率呈突飞猛进的趋势，占新发癌症病例的 2.8%。这种增长趋势在一定程度上得益于对亚临床状态的大量筛查。肿瘤的晚期生长是导致甲状腺癌相关死亡的主要原因。然而，其根本原因尚未完全揭示。最新的临床评估证实了几个主要的癌基因，如 RAS、BRAF 和 RET，它们是甲状腺癌发展和进展的关键驱动因素。BRAF 突变是甲状腺乳头状癌侵袭性肿瘤类型的主要原因，经常被报道。特征性的致癌变化意味着甲状腺癌在临床上是针对 RET、RAS 和 BRAF 突变的靶向治疗的理想模型。尽管灵敏的生化标志物检测已经得到改进，但甲状腺滤泡性肿瘤的诊断仍然是一个巨大的挑战，因为在 30%的病例中，活检抽吸无法确定肿瘤的性质。主要的障碍是辅助区分滤泡性甲状腺病变。滤泡性甲状腺腺瘤和癌在组织学上的区分是通过这种方式来完成的。这就严格要求识别灵敏的诊断/预后标志物，以降低甲状腺癌的风险，并避免不必要的活检和手术障碍。目前已有一系列预后生物标志物用于诊断甲状腺癌。然而，雌激素相关受体γ（ERRγ）在临床生物标志物中树立了新的基准。ERRγ 在甲状腺癌中的显著表达不仅使其自身成为一个特征性的诊断标志物，也使其成为一个治疗靶点。最近，我们报道 ERRγ 在 96 例甲状腺乳头状癌（PTC）和 26 例低分化/间变性甲状腺癌（ATC）样本中上调。各种合成的 ERRγ 反向激动剂，如 GSK5182、DN200434 和 24e，已被充分证明可调节 ATC 中 ERRγ 的表达，从而达到部分治愈。如果这一发现能够在更大的范围内进行检测，那么对这一标志物的评估可能是必要的和有意义的。本文综述了甲状腺癌临床生物标志物的研究进展。这也揭示了 ERRγ 作为甲状腺癌诊断和治疗靶点的临床重要性。
