title: Emerging therapeutics for advanced thyroid malignancies: rationale and targeted approaches.
abstract: BACKGROUND
  Thyroid cancer is an emerging public health concern. In the USA, its incidence has doubled in the past decade, making it the eighth most commonly diagnosed neoplasm in 2010. Despite this alarming increase, most thyroid cancer patients benefit from conventional approaches (surgery, radioiodine, radiotherapy, TSH suppression with levothyroxine) and are often cured. Nevertheless, a minority have aggressive tumors resistant to cytotoxic and other historical therapies; these patients sorely need new treatment options.
  
  
  METHODS
  Herein the biology and molecular characteristics of the common histological types of thyroid cancer are reviewed to provide context for subsequent discussion of recent developments and emerging therapeutics for advanced thyroid cancers.
  
  
  CONCLUSIONS
  Several kinase inhibitors, especially those targeting VEGFR and/or RET, have already demonstrated promising activity in differentiated and medullary thyroid cancers (DTC, MTC). Although of minimal benefit in DTC and MTC, cytotoxic chemotherapy with anti-microtubule agents and/or anthracyclines in combination with intensity-modulated radiation therapy appears to extend survival for patients with locoregionally confined anaplastic thyroid cancer (ATC), but to have only modest benefit in metastatic ATC. Further discovery and development of novel agents and combinations of agents will be critical to further progress in treating advanced thyroid cancers of all histotypes.
authors.affiliation: National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD 20892-7426, USA. harrispj@mail.nih.gov
authors.forename: Pamela Jo
authors.initials: PJ
authors.lastname: Harris
authors.forename: Keith C
authors.initials: KC
authors.lastname: Bible
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents