Targeted therapy of thyroid cancer

• Published in: Biochemical pharmacology 2010-09, Vol.80 (5), p.592-601
• Main Author: Sherman, Steven I.
• Format: Article
• Language: English
• Subjects: Angiogenesis inhibitors; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Epigenesis, Genetic - drug effects; Humans; Immunotherapy; Neovascularization, Pathologic - prevention & control; Protein kinase inhibitors; Protein Kinase Inhibitors - therapeutic use; Receptors, Cytoplasmic and Nuclear - drug effects; Thyroid carcinoma; Thyroid Neoplasms - blood supply; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - enzymology
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2010.05.003

Systemic chemotherapies for advanced or metastatic thyroid carcinomas have been of only limited effectiveness. For patients with differentiated or medullary carcinomas unresponsive to conventional treatments, novel therapies are needed to improve disease outcomes. Multiple novel therapies primarily targeting angiogenesis have entered clinical trials for metastatic thyroid carcinoma. Partial response rates up to 30% have been reported in single agent studies, but prolonged disease stabilization is more commonly seen. The most successful agents target the vascular endothelial growth factor receptors, with potential targets including the mutant kinases associated with papillary and medullary oncogenesis. Two drugs approved for other malignancies, sorafenib and sunitinib, have had promising preliminary results reported, and are being used selectively for patients who do not qualify for clinical trials. Additional agents targeting tumor vasculature, nuclear receptors, epigenetic abnormalities, and the immune response to neoplasia have also been investigated. Randomized trials for several agents are underway that may lead to eventual drug approval for thyroid cancer. Treatment for patients with metastatic or advanced thyroid carcinoma now emphasizes clinical trial opportunities for novel agents with considerable promise. Alternative options now exist for use of tyrosine kinase inhibitors that are well tolerated and may prove worthy of regulatory approval for this disease.