Repurposing drugs in endometrial cancer using genomic variants database

Abstract

Globally, endometrial cancer (EC) is the six most common cancers related to female reproductive. EC incidence and mortality rates have increased over the last decade. Cytotoxic therapy with carboplatin or paclitaxel is the recommended first-line treatment for EC patients. However, the options for following therapy are limited. The latest advances in molecular studies have uncovered the nature of genetic alterations in EC, compelling methods for further research into the treatment of EC since they may disclose to tailored pharmacological therapy. The aim of this study was to identify novel drug candidates in treating EC using genomics variants and biological pathway. The genomic variants of EC were downloaded from cBioportal database. We established connection between the biological EC risk genes from cBioportal database and the DrugBank database. Finally, we used Connectivity Map (CMap) analysis to identify possible drugs whose mechanisms coincided with therapeutic targets and rank them in accordance to scoring criteria. We identified novel conceivable candidate drugs for EC, they are Bosutinib, Acitretin and Nilutamide. These drugs exhibit robust scores in the CMap analysis compare to paclitaxel. We also discovered BCR-ABL1 and AR as potential biomarker-driven therapy in EC. This study demonstrates the possibility of using genetic network analysis combined with bioinformatics to repurpose drugs for the treatment of EC. Further investigation will be undertaken to explore the mechanisms involved in the application of BCR-ABL1 and AR for treating of EC.

Keywords

• acitretin
• bosutinib
• drug reporpusing
• endometrial cancer
• genomics variants
• nilutamide