Unfolding of Imminent Bio-Signatures in the Prognosis of Thyroid Cancer - The Emergence of Estrogen Related Receptor Gamma (ERRγ) as a Hurricane

Sep 24, 2026

Uploaded by Patrick

Thyroid cancer incidence has risen markedly, and late tumor progression remains a principal cause of thyroid cancer mortality despite expanded screening and improved biochemical assays. Current clinical insights highlight key oncogenic drivers such as RAS, BRAF, and RET, yet diagnostic uncertainty persists, particularly in distinguishing follicular lesions and biopsy-limited follicular neoplasms. This review emphasizes Estrogen Related Receptor Gamma (ERRγ) as a high-impact diagnostic marker and therapeutic target.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Introduction

Thyroid cancer subtypes and diagnostic challenge

Biomarkers and clinical utility

Molecular profiling and screening models

REVIEW Editorial Process: Submission:08/09/2022 Acceptance:02/20/2023 Unfolding of Imminent Bio-Signatures in the Prognosis of Thyroid Cancer; The Emergence of Estrogen Related Receptor Gamma (ERRγ) as a Hurricane Deepak Gulwani1, Priyanka Upadhyay1, Ridhima Goel1, Vijaya Sarangthem2, Thoudam Debraj Singh1 * Abstract 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 tobe 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 ofERRγ 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 ofERRγ as an evolving diagnostic and therapeutic target in thyroid cancer. Keywords: ERRγ -thyroid cancer-genetic mutations-Lnc RNA-miRNA-biomarkers-Agonist/Inverse agonist Asian Pac J Cancer Prev, 24 (2), 375-387 Introduction Thyroid cancer has become the most common endocrine disorder in the past few years (Chen et al., 2009) . Depending on its origin, most thyroid cancers are derived from follicular epithelial cells such as papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and Hurthle cell carcinoma. These cells are characterized as well-differentiated cancer, while anaplastic thyroid cancer (ATC) is a form of undifferentiated cancer. Notably, ATC is highly lethal in all forms. The inefficient diagnostic tools and partial knowledge of molecular mechanistic are predicted to be the prime reason for the failure of the clinical cure for PTC and ATC (Cabanillaset al., 2016) . Therefore, a better understanding of the signalling pathways during thyroid cancer development and progression has stimulated interest in the identification of biomarkers. These sensitive biomarkers may catalyze the speed of prediction in cancer progression and thus may enable clinicians to decide the most appropriate course of treatment. The biomarkers define the effectiveness of surgery, chemotherapy, and radioiodine ablation. The progression i

FAQs

Why is diagnosis of thyroid cancer still challenging despite screening?

Diagnostic tools cannot fully define tumor nature in a substantial fraction of cases, and distinguishing between follicular thyroid lesions remains difficult even with histology. This creates a need for sensitive diagnostic and prognostic markers to reduce reliance on difficult biopsy and surgery.

Which molecular drivers are discussed as key drivers in thyroid cancer progression?

The text highlights oncogenes including RAS, BRAF, and RET as major drivers associated with development and progression. It also notes BRAF mutation as a common cause of aggressive tumor types in papillary thyroid carcinoma.

How does ERRγ relate to thyroid cancer diagnosis and treatment?

ERRγ shows dramatic expression in thyroid cancer, supporting its role as both a characteristic diagnostic marker and a therapeutic target. The article further reports that synthetic ERRγ inverse agonists can modulate ERRγ expression in certain thyroid cancer samples.

Sep 24, 2026

Uploaded by Patrick