Target-based drug repositioning in papillary renal cell carcinoma with TFE3 fusion

Papillary renal cell carcinoma (PRCC) is the second most common subtype of renal cell carcinoma. Recurrent transcription factor E3 (TFE3) fusions have been identified in PRCC. Although patients with TFE3 fusions show relatively aggressive phenotypes, no effective targeted therapies have been developed. In this study, we aimed to identify putative therapeutic targets through systematic bioinformatic analysis of PRCC with TFE3 fusion. We identified TFE3 fusion cases (n = 6) and controls (n = 282) in The Cancer Genome Atlas database. A total of 1,314 differentially expressed genes were extracted. An overrepresentation analysis revealed cancer-related signaling pathways, which were categorized to 13 cancer-related pathways, including nuclear factor-erythroid factor 2-related factor 2 (NRF2)-, G protein-coupled receptor (GPCR) signaling-, inflammatory response-, development-, and insulin-like growth factor-related pathways. A network analysis and literature review were performed using drug-target databases to identify putative applicable drugs. We identified several promising drug candidates for PRCC with TFE3 fusion, including amrubicin, BCL6 inhibitors (79-6, BI-3812), cetuximab, epirubicin, gemcitabine, ipilimumab, linsitinib, olaparib, Orencia, paclitaxel, panitumumab, sorafenib, and tamoxifen. Our suggested strategy can help bridge the gap between transcriptome studies and the choice of therapeutic agents. Further experimental validation is needed to improve the efficacy of precision medicine for PRCC.