Dual inhibition of mitogen-activated protein kinase kinase and mammalian target of rapamycin in differentiated and anaplastic thyroid cancer.

摘要: Context: Differentiated thyroid cancer and anaplastic tumors frequently have activation of the ras/raf /MAPK kinase (MEK)/ERK phosphatidylinositol 3-kinase (PI-3K)/AKT/mammalian target rapamycin (mTOR) signaling pathways. Objective: The objective study was to investigate efficacy MEK mTOR inhibitors in preclinical treatment models with defined mutation status. Experimental Design: inhibitor AZD6244 (ARRY-142886) were tested separately combination 10 differentiated cell lines a xenograft model for evidence pathway inhibition, growth apoptosis, long-range adaptation resistance. Results: Seven had significant basal activity PI-3K/AKT/mTOR pathway, elevated phosphorylated AKT p70 S6 kinase. Activation ras/RAF/MEK/ERK equally common this panel. All exhibite...