In spite of the good prognosis of thyroid carcinoma (TC), a metastatic disease is
developed by approximately 5% of patients, not responsive to radioactive iodine (RAI),
and with a more aggressive behaviour. The absence of specific and effective drugs for
aggressive TC leads to the need of new efforts towards new drugs development.
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 of
inducing 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.
Keywords: Anaplastic thyroid cancer, BRAF mutations, cabozantinib, CLM3,
CLM94, differentiated thyroid cancer, follicular thyroid cancer, H-RAS
mutations, K-RAS mutations, lenvantinib, medullary thyroid cancer, N-RAS
mutations, papillary thyroid cancer, pyrazolpyrimidine, Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, RET
mutations, sorafenib, telomerase reverse transcriptase (TERT) mutations,
vandetanib, vascular endothelial growth factor receptor 2.