These data suggest that targeting angiogenesis pathways and specifically the VEGF pathway may represent a novel therapeutic approach in the treatment of MTC.
Recently, vandetanib (ZD6474), an inhibitor of vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR 3, RET, and epidermal growth factor receptor (EGFR), was approved for the treatment of adults with symptomatic or progressive MTC.
Mutations in the RET proto-oncogene and vascular endothelial growth factor receptor (VEGFR) activity are critical in the pathogenesis of medullary thyroid cancer (MTC).
We report here a rapid response to a sorafenib (RET and RAF kinase and vascular endothelial growth factor receptor inhibitor)--based regimen in a patient with sporadic MTC who had advanced, progressive disease and a novel RET kinase aberration at exon 11 shown in tumor tissue.
In a cell culture model of MTC, exogenous trkB expression resulted in severely impaired tumorigenicity and was associated with 11-fold lower levels of the angiogenesis factor vascular endothelial growth factor.