THYROID AND PARATHYROID DISEASES: DIAGNOSIS, TREATMENT AND SURGERY WITH CURRENT APPROACHES

thyroid_and_parathyroid_diseasesnevinsakoglukapak1-0-25

THE PAST, PRESENT AND FUTURE OF GENETIC AND MOLECULAR APPROACHES TO THYROID DISEASES

Abdullah As

İstanbul Health and Technology University, Faculty of Medicine, Department of General Surgery, İstanbul, Türkiye

As A. The Past, Present and Future of Genetic and Molecular Approaches to Thyroid Diseases. Kesici U, ed. Thyroid and Parathyroid Diseases: Diagnosis, Treatment and Surgery with Current Approaches. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.79-101.

ABSTRACT

Thyroid cancer (TC) diagnosis and treatment have significantly advanced through genetic and mo- lecular research. Molecular tests, such as Afirma, ThyroSeq, and MPTX play a crucial role in differ- entiating benign from malignant thyroid nodules (TNs), thus reducing unnecessary surgeries. These molecular panels identify gene mutations and fusions in critical genes like BRAF, RAS or RET; and molecular alterations as in microRNAs (miRNAs). Thus they provide valuable information about tu- mor behavior and help guide treatment decisions. Despite their potential, the integration of genetic and molecular biomarkers into routine clinical practice, still remains a challenge. MiRNAs, small non-coding RNA molecules, have garnered attention for their role in regulating gene expression and influencing tumorigenesis. In TC, miRNAs such as miR-146b, miR-221, and miR-222 are commonly upregulated, particularly in papillary thyroid carcinoma (PTC). These miRNAs modulate tumor pro- gression by targeting tumor suppressors and activating oncogenic pathways, such as MAPK and AKT. Profiling miRNAs offers a promising diagnostic approach and can help predict prognosis, especially in aggressive or radioactive iodine-resistant (RAIR) TCs. Targeted therapies have played an important role in TC treatment. Tyrosine kinase inhibitors (TKIs), for example, have demonstrated efficacy in tumors with specific mutations like those in the RET or MEK pathways. Ongoing research are focused on discovering new mutations to enable more precise and personalized treatments, particularly for advanced or resistant cancers. Nanomedicine (NM) has become a powerful tool in cancer treatment, particularly for targeted drug delivery and diagnostic applications. Nanoparticles (NPs) can be engi- neered to selectively target tumor cells, improving treatment precision and minimizing side effects. This technology enhances the effectiveness of chemotherapy and diagnostic imaging, making it an essential component of personalized cancer care in near future. Artificial intelligence (AI) is enhancing TC diagnostics by analyzing complex datasets from imaging and pathology. AI algorithms assist in identifying actionable mutations and predicting treatment responses, advancing personalized care strat- egies. In conclusion, advancements in the understanding of genetic mutations and molecular alterations in TC have transformed the diagnosis and treatment landscape. Genetic and molecular testing, along with targeted therapies and miRNA profiling, have paved the way for more personalized and effective treatments. Although challenges remain, continued progress in these areas holds promising potential for improving TC patient outcomes.

Keywords: Thyroid nodule; Thyroid cancer; Genetic mutation; Molecular biomarker; MicroRNA; Molecular test panel; Targeted therapy; Nanoparticule

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