S1.3 - Targeted therapy in radioiodine refractory thyroid cancer

Abstract

Radioiodine-refractory thyroid cancer (RAIR-TC) represents a challenging subset of differentiated thyroid cancers characterized by loss of iodine avidity and poor or absent response to conventional radioactive iodine therapy. Over the past decade, advances in molecular biology have significantly improved the understanding of the genetic alterations driving these tumors, leading to the development of targeted therapeutic strategies. Key oncogenic pathways implicated in RAIR-TC include mutations in BRAF, RAS, RET/PTC rearrangements, and alterations in the MAPK and PI3K-AKT signaling pathways. Targeted therapies, particularly tyrosine kinase inhibitors (TKIs), have emerged as the cornerstone of treatment for patients with progressive RAIR-TC. Agents such as lenvatinib and sorafenib have demonstrated improved progression-free survival by inhibiting multiple kinases involved in tumor proliferation and angiogenesis, including VEGFR, FGFR, and RET. More recently, selective inhibitors targeting specific genetic alterations, such as BRAF and RET inhibitors, have shown promising efficacy with improved safety profiles compared to multikinase inhibitors. Despite these advances, challenges remain, including the development of resistance, treatment-related toxicities, and variability in patient response. Ongoing research is focused on combination therapies, redifferentiation strategies to restore radioiodine uptake, and the identification of predictive biomarkers to guide personalized treatment. In conclusion, targeted therapy has transformed the management of RAIR-TC, offering meaningful clinical benefit. Continued investigation into tumor biology and therapeutic optimization is essential to further improve outcomes in this aggressive disease subset.