title: Novel molecular targeted therapies for refractory thyroid cancer.
abstract: The incidence of thyroid cancer continues to increase and this neoplasia remains the most common endocrine malignancy. No effective systemic treatment currently exists for iodine-refractory differentiated or medullary thyroid carcinoma, but recent advances in the pathogenesis of these diseases have revealed key targets that are now being evaluated in the clinical setting. RET (rearranged during transfection)/PTC (papillary thyroid carcinoma) gene rearrangements, B-Raf gene mutations, and vascular endothelial growth factor receptor 2 (VEGFR-2) angiogenesis pathways are some of the known genetic alterations playing a crucial role in the development of thyroid cancer. Several novel agents have demonstrated promising responses. Of the treatments studied, multi-kinase inhibitors such as axitinib, sorafenib, motesanib, and XL-184 have shown to be the most effective by inducing clinical responses and stabilizing the disease process. Randomized clinical trials are currently evaluating these agents, results that may soon change the management of thyroid cancer.
authors.affiliation: Cleveland Clinic Florida, Weston, Florida, USA.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Perez
authors.forename: Edgardo S
authors.initials: ES
authors.lastname: Santos
authors.forename: Belisario A
authors.initials: BA
authors.lastname: Arango
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000813:Anilides / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077784:Axitinib; D001549:Benzamides; D001557:Benzenesulfonates / Q000627:therapeutic use; D016227:Benzoquinones / Q000627:therapeutic use; D001632:Bibenzyls / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D047630:Depsipeptides / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D000068877:Imatinib Mesylate; D007093:Imidazoles / Q000627:therapeutic use; D007191:Indazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D047029:Lactams, Macrocyclic / Q000627:therapeutic use; D000077269:Lenalidomide; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009841:Oligonucleotides; D010671:Phenylurea Compounds / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors; D011719:Pyrazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D014635:Valproic Acid / Q000627:therapeutic use; D000077337:Vorinostat
chemical_list: D020533:Angiogenesis Inhibitors; D000813:Anilides; D000970:Antineoplastic Agents; D001549:Benzamides; D001557:Benzenesulfonates; D016227:Benzoquinones; D001632:Bibenzyls; D001897:Boronic Acids; D047630:Depsipeptides; D018841:HSP90 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D047029:Lactams, Macrocyclic; D009841:Oligonucleotides; D010671:Phenylurea Compounds; D010879:Piperazines; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D011799:Quinazolines; D011804:Quinolines; D013449:Sulfonamides; C558660:cabozantinib; D009536:Niacinamide; C112765:tanespimycin; D013792:Thalidomide; D000077337:Vorinostat; D014635:Valproic Acid; D000069286:Bortezomib; C040105:combretastatin; C516667:pazopanib; D000068877:Imatinib Mesylate; D000077157:Sorafenib; D000077784:Axitinib; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; C531958:lenvatinib; D000077269:Lenalidomide; C519562:imetelstat; D000077156:Gefitinib; D000077210:Sunitinib; C452423:vandetanib