Computational repositioning and preclinical validation of pentamidine for renal cell cancer.

ABSTRACT: Although early stages of clear cell renal cell carcinoma (ccRCC) are curable, survival outcome for metastatic ccRCC remains poor. We previously established a highly accurate signature of differentially expressed genes that distinguish ccRCC from normal kidney. The purpose of this study was to apply a new individualized bioinformatics analysis (IBA) strategy to these transcriptome data in conjunction with Gene Set Enrichment Analysis of the Connectivity Map (C-MAP) database to identify and reposition FDA-approved drugs for anticancer therapy. Here, we demonstrate that one of the drugs predicted to revert the RCC gene signature toward normal kidney, pentamidine, is effective against RCC cells in culture and in a RCC xenograft model. ccRCC-specific gene expression signatures of individual pat

SUBMITTER: Zerbini LF 

PROVIDER: S-EPMC4090263 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature