Integrated Genomic Analysis to Identify Druggable Targets for Pancreatic Cancer

Pancreatic cancer (PC) is one of the leading causes of death globally, and it is currently the sixth deadliest cancer-related disease. The standard treatment for PC usually involves the use of gemcitabine in conjunction with other chemotherapeutic medicines, as per the guidelines set forth by the National Comprehensive Cancer Network (NCCN). However, drug resistance to this treatment remains a significant challenge, resulting in ineffective PC management. We exploited genomic data from PC-associated and drug target genes for possible medication repurposing to accelerate drug discovery and investigate alternate approaches for PC treatment. For this investigation, we used somatic mutation gene data for PC from the cBioPortal, a publicly accessible cancer genomics database. The Biological Process (BP), Knock Out Mouse (KO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene List Automatically Derived for You (GLAD4U), and Gene Omnibus Dataset Series (GSE) are the annotations that were utilizaed to rank the genes linked with PC-associated genes. Genes with a score of 2 in these functional annotations were labeled as biological PC risk genes. Subsequently, to find possible therapeutic targets, we matched these biological PC-risk genes to the DrugBank database. We used CMap Touchstone analysis to further refine our selection, utilizing gemcitabine's profile in the MCF7 cell line as the standard treatment for PC. This analysis led to the identification of 13 promising PC candidate drugs. Notably, eight of these drugs were already undergoing clinical trials, two were in the pre-clinical study phase, and three lacked evidence status. Two of the identified drugs—fulvestrant, which targets ESR1, and midostaurin, which targets PRKA—came to light as promising candidates for PC treatment via genomic-driven drug repurposing. In conclusion, our research has shown that our pipeline is solid, enabling us to acquire more drugs for clinical studies. Furthermore, we propose midostaurin and fulvestrant as promising drug repurposing options for PC treatment.