Tyrosine kinase inhibitors. Therapies for thyroid cancer

Several genetic alterations in different molecular pathways in TC have been shown in the last decades, associated with TC development and progression. Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, RET mutations,BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the studied pathways, determinant in TC development. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the above-mentioned molecular pathways involved in growth, angiogenesis, local and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC), and they have been shown capable ofinducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for MTC treatment; sorafenib and lenvatinib have been approved for DTC refractory to RAI. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds, and to personalize the therapy in each TC patient.