Standard and emerging therapies for metastatic differentiated thyroid cancer

Differentiated thyroid cancer accounts for >90% of cases of thyroid cancer, with most patients having an excellent prognosis. Distant metastases occur in 10%-15% of patients, decreasing the overall 10-year survival rate in this group to 40%. Radioactive iodine has been the mainstay of treatment for distant metastases, with good results when lesions retain the ability to take up iodine. For patients with metastatic disease resistant to radioactive iodine, treatment options are few and survival is poor. Chemotherapy and external beam radiotherapy have been used in these patients, but with disappointing results. In recent years, our understanding of the molecular pathways involved in thyroid cancer has increased and a number of molecular targets have been identified. These targets include the proto-oncogenes BRAF and RET, known to be common mutations in thyroid cancer; vascular endothelial growth factor receptor and platelet-derived growth factor receptor, associated with angiogenesis; and the sodium-iodide symporter, with the aim of restoring its expression and hence radioactive iodine uptake. There are now multiple trials of tyrosine kinase inhibitors, angiogenesis inhibitors, and other novel agents available to patients with metastatic thyroid cancer. This review discusses both traditional and novel treatments for metastatic differentiated thyroid cancer with a particular focus on emerging treatments for patients with radioactive iodine-refractory disease.