Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts

a Heatmap of proteins associated with resistance in 786-O RCC xenograft mouse model. Rows depict proteins altered during resistance, and columns depict individual replicates of untreated, day 3, and resistant tumors. Relative protein expression is shown in pseudocolor, where green represents down- regulation, and red represents up-regulation. b Venn Diagram (above) and heatmap (below) of proteins whose altered expression is associated with sunitinib resistance in 786-O and A498 RCC xenograft mouse models. Altered expression of six of these proteins (depicted in heatmap) is associated with sunitinib resistance in both models. c Integrative systems biology analysis of proteome and transcriptome data to identify key drivers of resistance. Each node represents a gene or protein; edges represent interaction between genes or proteins. Node color intensity indicates degree of upregulation (red) and downregulation (green) during resistance compared to day 3 responding or untreated samples. d Immunoblot analysis of CTSB expression in 786-O xenograft tumor lysates from untreated mice or from mice showing resistance to sunitini