New Targeted Therapies for Anaplastic Thyroid Cancer

Alessandro      Antonelli; Poupak      Fallahi; Salvatore      Ulisse; Silvia      Martina Ferrari; Michele      Minuto; Giovanna      Saraceno; Francesca      Santini; Valeria      Mazzi; Massimo      D'Armiento; Paolo      Miccoli

doi:10.2174/187152012798764732

Abstract

Anaplastic thyroid cancer (ATC) is often incurable because it doesnt respond to radioiodine, radiotherapy or chemotherapy, and new therapeutic approaches are needed. Peroxisome proliferator-activated receptor-gamma (PPARg) gene and protein are present in ATC cells, and PPARg ligands inhibit cell proliferation, induce apoptosis, and also down regulate the invasive potential of ATC cells. Also, inhibitors of the Aurora serine/threonine kinases have antineoplastic effect on ATC cells in vitro and on ATC xenografts. Tyrosine kinases inhibitors are actually under evaluation for the treatment of ATC, for example imanitib or sorafenib. Other studies have focused on evaluating antiangiogenic agents for treatment of ATC. These agents include: combretastatin A4 phosphate, aplidin, PTK787/ZK222584, and human VEGF monoclonal antibodies (bevacizumab, cetuximab). Small-molecule adenosine triphosphate (ATP) competitive inhibitors directed intracellularly at epidermal growth factor receptor (EGFR)s tyrosine kinase, such as erlotinib, or gefitinib are also under evaluation. The development of drugs that have multiple therapeutic targets and the utilization of multiple cancer-targeting agents are both emerging strategies for ATC treatment. For example, a preclinical study evaluated the activity of a dual inhibitor of EGFR and vascular endothelial growth factor (VEGF), NVP-AEE788, alone and in combination with paclitaxel for the treatment of ATC. Even if new therapeutic approaches against ATC are under development, more research is needed to finally identify therapies able to control and to cure this disease. The possibility of testing the sensitivity of primary ATC cells from each subject to different drugs could increase the effectiveness of the treatment in the next future.

Keywords: Anaplastic thyroid cancer, Anti-angiogenetic drugs, Dedifferentiated thyroid cancer, Inhibitor of the Aurora serine/threonine kinases, Papillary thyroid cancer, Pioglitazone, Rosiglitazone, Tyrosine kinase inhibitors, AGONISTS, kinase