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.
Mutations in the RET proto-oncogene and vascular endothelial growth factor receptor (VEGFR) activity are critical in the pathogenesis of medullary thyroid cancer (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.
These data suggest that targeting angiogenesis pathways and specifically the VEGF pathway may represent a novel therapeutic approach in the treatment of 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.