Traditional clinicopathologic risk assessment of thyroid cancer has often been inaccurate, leading to both overtreatment of low-risk cases and under-treatment of potentially aggressive ones. However, significant advancements in our understanding of the molecular landscape of TC over the past decade have ushered in a new era of precision medicine. Molecular-based risk stratification, utilizing genetic mutations, is guiding clinical decision-making with greater accuracy, though its full potential remains limited by the complexity of mutation interactions and their variable prognostic significance.
The BRAFV600E mutation, the most extensively validated biomarker in TC, is a reliable predictor of malignancy, but it should not be used as an independent prognostic factor. RAS mutations, the second most common in TC, are found in both benign and malignant lesions, complicating their prognostic utility. RET fusions and other receptor tyrosine kinase rearrangements are observed in a subset of tumours lacking BRAF or RAS mutations, with RET mutations being particularly relevant in medullary thyroid cancer, where they play a critical role in pathogenesis and can guide targeted therapy.
Importantly, co-occurring mutations with BRAF or RAS—such as those in the TERT promoter, PIK3CA, TP53, or EIF1AX—are emerging as strong predictors of aggressive disease and poor outcomes. These molecular markers are refining risk stratification and enabling more tailored clinical management.
Additionally, novel technologies like single-cell RNA sequencing are revealing tumour heterogeneity, while liquid biopsy of circulating cell-free DNA is enhancing non-invasive disease monitoring. These advances hold great promise for real-time tracking of tumour evolution and treatment response, transforming the management of thyroid cancer.
This talk will provide a comprehensive overview of these emerging biomarkers and technologies, the current state of the field, and the exciting developments on the horizon that will further enhance TC precision medicine.