Activating the Wnt/β-Catenin Pathway for the Treatment of Melanoma – Application of LY2090314, a Novel Selective Inhibitor of Glycogen Synthase Kinase-3
Fig 5
LY2090314 elevates Axin2 gene expression in vivo, demonstrates single agent activity in the A375 xenograft model of melanoma and enhances the efficacy of DTIC.
A. Plasma PK of LY2090314 in non-tumor bearing mice. B. A single dose of LY2090314 (25mg/kg) elevates Axin2 gene expresion in vivo, a marker of wnt pathway activation. C. Subcutanous A375 xenografts were treated with 25mg/kg LY2090314 Q3D and resulted in a significant tumor growth delay (p<0.006). D. LY2090314 (2.5mg/kg Q3D) enhances the efficacy of DTIC (60mg/kg QD) in A375 xenografts (p< 0.02).