Targeting vascular endothelial growth factor receptor in thyroid cancer: the intracellular and extracellular implications.
Our understanding of the molecular pathophysiology of differentiated thyroid cancer (DTC) has developed considerably over the last 10 years. Aberrant signaling through B-Raf and Akt has been implicated in the tumorigenesis of DTC. Moreover, these highly vascular tumors have proven to be sensitive to the inhibition of vascular endothelial growth factor receptor (VEGFR-2). It is likely that the multikinase inhibitors, sorafenib, sunitinib, axitinib, and motesanib, whose targets include VEGFR-2, exert their effects primarily through inhibition of endothelial cells. However, as VEGFR-2 is expressed on DTC cells, these compounds may have direct antitumor action. This review will discuss the key signaling pathways involved in thyroid cancer and their implications for targeted therapy.
Keefe
Stephen M
SM
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Cohen
Marc A
MA
Brose
Marcia S
MS
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates; D016503:Drug Delivery Systems; D006801:Humans; D020935:MAP Kinase Signaling System; D009536:Niacinamide / Q000031:analogs & derivatives; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010671:Phenylurea Compounds; D011725:Pyridines; D015398:Signal Transduction / Q000187:drug effects*; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D040301:Vascular Endothelial Growth Factor Receptor-2; D051058:Oncogene Protein v-akt