Multikinase inhibitors and thyroid cancer

Somatic RET mutations are frequently found in medullary thyroid cancers (MTCs), highlighting RET as a potential therapeutic target. Tyrosine kinase inhibitors such as vandetanib inhibit RET and other kinases. Vitagliano and colleagues studied the mechanism of action of vandetanib in human MTC cells with oncogenic RET mutations. They found that vandetanib reduced MTC cell proliferation, inhibited proliferation and phosphorylation of the Shc/MAPK pathway and inhibited vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) kinases. Over-stimulating EGFR resulted in a partial rescue when RET activity was inhibited, showing that vandetanib simultaneously inhibits multiple kinases. Vitagliano et al. (2011) Endocrine-Related Cancer 18 1–11.

Read the full article at DOI: 10.1677/ERC-09-0292.