Furthermore, Nintedanib, which blocks VEGFR2, RET, ERK1,2 and PI3K/AKT/FOXO1 like Vandetanib, also inhibits PI3K/AKT/mTOR, but may still have limited long-term anti-tumor effects on MTC due to the development of resistance. This evidence concerns the gene MAPK3 and medullary thyroid gland carcinoma.