Identification of potential drug candidates for the treatment of triple-negative breast cancer

Triple-negative breast cancer (TNBC) occurs in nearly 20% of patients diagnosed with breast cancer (BC). It is a subtype of BC that lacks expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptors. TNBC is highly aggressive in nature and is clinically challenging. However, developing new drugs is time consuming with high failure rates. Thus to overcome these difficulties, drug repurposing has been proposed. Drug repurposing is a process of finding new therapeutic indications for existing drugs to improve drug productivity and to utilize their full potential. In our study, we collected and used 1075 differentially expressed genes (DEGs) and significant hub genes of TNBC from our previous research. Drug repurposing tools such as CMap, sscMap, SPIED3, and LINCS-L1000 CDS2 were employed to screen the drug candidates for DEGs. Subsequently, the binding affinity between drug candidates and TNBC-associated hub genes was calculated using molecular docking. In addition, for the shortlisted drugs, we collected the known target genes from STITCH and DrugBank databases and found there to be slight overlap with the hub genes. Further, to study the important functions and the pathways of DEGs, enrichment analysis was performed using the Enrichr tool. On the basis of the scores obtained, 31 drugs were found to be promising to repurpose for the treatment of cancer. Also, it is evident from the docking studies that dabrafenib and MAPK1 exhibited the best binding energy of − 9.9 kcal/mol. From the reported literature, it is noted that the aforementioned drugs used for the treatment of different cancers are found to be repurposed for other cancers as well. The analysis of pathways and ontologies showed that DEGs are highly enriched in biological processes such as cell division, proliferation, DNA replication, and cancer-related pathways. Thus, this study may facilitate finding new indications for existing drugs for the treatment of cancer.