Thyroid cancer: pathogenesis and targeted therapy.

Therapeutic options for advanced, unresectable radioiodine-resistant thyroid cancers have historically been limited. Recent progress in understanding the pathogenesis of the various subtypes of thyroid cancer has led to increased interest in the development of targeted therapies, with potential strategies including angiogenesis inhibition, inhibition of aberrant intracellular signaling in the MAPK and PI3K/AKT/mTOR pathways, radioimmunotherapy, and redifferentiation agents. On the basis of a recent positive phase III clinical trial, the RET, vascular endothelial growth factor receptor (VEGFR), and epidermal growth factor receptor (EGFR) inhibitor vandetanib has received FDA approval as of April 2011 for use in the treatment of advanced medullary thyroid cancer. Several other recent phase II clinical trials in advanced thyroid cancer have demonstrated significant activity, and multiple other promising therapeutic strategies are in earlier phases of clinical development. The recent progress in targeted therapy is already revolutionizing management paradigms for advanced thyroid cancer, and will likely continue to dramatically expand treatment options in the coming years.