Logic-Based Modeling and Drug Repurposing for the Prediction of Novel Therapeutic Targets and Combination Regimens Against E2F1-Driven Melanoma Progression

The study focuses on combating E2F1-driven melanoma progression by using logic-based modeling and drug repurposing. Researchers integrated an E2F1-mediated epithelial-mesenchymal transition (EMT) map with transcriptomics data from melanoma cells to reconstruct a core regulatory network. Through in silico perturbation experiments, they found that targeting Protein kinase B (AKT1) and oncoprotein murine double minute 2 (MDM2) significantly reduces EMT in melanoma. Virtual screening of FDA-approved drugs identified Cialis and Finasteride as potent inhibitors of AKT1 and MDM2, respectively. These findings suggest that these drugs could be repurposed for treating aggressive melanoma.