Therapeutic Potential of Tyrosine Kinase Inhibitors in Advanced Thyroid Cancer

Tyrosine kinase inhibitors (TKIs) have become essential agents for managing advanced thyroid cancers, particularly refractory cases that do not respond to conventional therapies. This review emphasizes the key molecular drivers and oncogenic pathways (including the mitogen-activated protein kinase (MAPK) signaling pathway) that are therapeutically targetable, providing the rationale for TKI intervention and unraveling the role of key receptor tyrosine kinases, including VEGFR, PDGFR, and EGFR, in the pathogenesis and progression of thyroid cancer. Recent studies comparing multikinase and selective TKIs show distinct differences in efficacy, toxicity, and therapeutic use across thyroid cancer subtypes. FDA-approved TKIs provide clear clinical benefit, but challenges such as drug resistance, limited response durability, and treatment-related toxicities persist. Emerging next-generation inhibitors, pathway-specific approaches, and combination strategies are being developed to address these limitations. TKI therapy has significantly improved outcomes for patients with advanced thyroid cancers by targeting central molecular pathways that drive tumor growth and survival. While resistance and toxicity continue to restrict optimal long-term benefit, ongoing developments in precision oncology and targeted therapeutics offer promising avenues to refine and enhance TKI-based treatment strategies in the near future.