Targeted therapies for advanced thyroid cancer.
OBJECTIVE
Thyroid cancer incidence has significantly increased and the majority of cases are represented by differentiated thyroid carcinomas that are characterized by a very good prognosis. Nevertheless, after initial treatment up to 15% of patients present disease persistence or relapse and those with locally advanced or metastasized cancers that do not respond to established therapies ultimately risk death. This scenario has started to change following the development of molecular targeted therapies. This review will focus on the principles behind the use of these novel therapies and on the results of the most recent clinical trials with tyrosine kinase inhibitors (TKIs) and other targeted therapies in thyroid cancer.


RESULTS
An understanding of the molecular events involved in cancer formation has prompted the development of numerous drugs that target key molecules implicated in angiogenesis and in the maintenance of the malignant phenotype of cancer cells. The results of several phase I and phase II studies and one phase III trial testing the efficacy of these drugs in advanced thyroid cancer are now available.


CONCLUSIONS
Among the tested drugs, the TKIs sorafenib for differentiated thyroid carcinoma and vandetanib and XL184 for medullary thyroid carcinoma appear very effective and have reached phase III clinical trials. Second-generation TKIs and selective kinase inhibitors are showing even more promising profiles. Improved knowledge of the targets of the different drugs, combined with molecular profiling of the tumors to treat, will allow a tailored pharmacogenomic approach.
Department of Internal Medicine, University of Perugia, Perugia, Italy. efisio.puxeddu@unipg.it
Efisio
E
Puxeddu
Serena
S
Romagnoli
Massimo Eugenio
ME
Dottorini
D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology
D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases