Drug Repositioning Study in Search of Potent Inhibitors Blocking Multiple Pathways for the Treatment of Breast Cancer

Abstract Breast cancer is most malignant cancer in women worldwide. The efforts are going on for improvement in patient’s survival and treatment strategies. The goal of the present work is to find out connections among drugs-genes-breast cancer and to re-purpose approved drugs for the treatment of breast cancer. In this context, the gene expression data of breast cancer samples was analyzed to identify the upregulated/downregulated genes in different clinical stages of breast cancer. A large number of genes were found to be upregulated/downregulated in different clinical stages of breast cancer. Some of the genes were found to be stage specific and some were common to all stages. The biological pathways were studied in early and late stages of breast cancer, which indicated that pathways as Methylglyoxal Degradation I, Catecholamine biosynthesis and Serotonin/Melatonin biosynthesis were enriched in early stage and pathways as Matrix metalloproteases, Airway pathology in COPD, Glycogen degradation II and Glycogen degradation III were enriched in late stages of breast cancer. The drug repurposing analysis revealed that the different classes of drugs as enzyme inhibitors, CNS agents, Glucocorticoids, insulin sensitizers, tubulin inhibitors, adhesion inhibitors showed strong connections with MCF7 cell line. Further, it was found that the drugs as Nortriptyline, AZD-6482, Acitretin and GW-507 were found to target multiple genes in interleukin pathway, enzymatic pathway and GPCR signaling pathway and drugs as Caffeine, Canertinib and Triciribine was found to target multiple genes which were dysregulated and involved in interleukin pathway, enzymatic pathway, GPCR signaling pathway and metabolic pathways.