title: The discovery and development of vandetanib for the treatment of thyroid cancer.
abstract: BACKGROUND
  Thyroid cancer represents over 90% of all endocrine malignancies, with medullary thyroid carcinoma (MTC) accounting for 5 - 9% of them. Patients with early-stage disease have a favorable prognosis, but once distant metastasis develops, survival drops to 50% or less. Although surgery remains effective for early-stage disease, patients with advanced disease pose a challenge as traditional therapies have not provided long-term benefits. Vandetanib, initially developed to target other receptors, demonstrated anti-rearranged during transfection (anti-RET) kinase activity. This led to preclinical studies followed by recent human clinical trials, culminating in its FDA approval in April 2011 for application in the treatment of symptomatic or progressive MTC in patients with surgically unresectable, locally advanced or metastatic disease.
  
  
  METHODS
  The authors provide a review of the discovery strategy and preclinical development of vandetanib. The authors also provide some insight into the clinical development and the drug's post-launch situation.
  
  
  CONCLUSIONS
  Vandetanib has been shown to improve progression-free survival in MTC patients, but its impact on overall survival is still inconclusive. Further data analysis will be needed to answer the question of whether it impacts overall survival in MTC. Despite its advancements, vandetanib still lacks durable efficacy, carries moderate toxicity and has issues with drug resistance over time, not to mention issues of cost. There is a significant need for additional research to discover and develop improved therapeutic strategies for this difficult disease.
authors.affiliation: University of Michigan Health System, Department of Otolaryngology - Head and Neck Surgery , 1500 E. Medical Center Drive, 1904 Taubman Center, Ann Arbor, MI 48109-1274 , USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sim
authors.forename: Mark Steven
authors.initials: MS
authors.lastname: Cohen
mesh_terms: D018572:Disease-Free Survival; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D010880:Piperidines / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D010880:Piperidines; D011799:Quinazolines; C452423:vandetanib