Deciphering the Intricacies of Breast Cancer Signaling Network and the Potential of Soy-derived Isoflavones on Cancer Therapeutics

Background Breast cancer remains a significant global health challenge despite the emergence of various drug molecules. However, the adverse side effects of several drugs and chemotherapy necessitate the exploration of novel therapeutic strategies. Identifying effective therapeutic proteins specific to breast cancer is complex, and finding potential natural, non-cytotoxic inhibitors presents an even more significant challenge in this field. Objectives In this study, we aimed to identify various proteins responsible for the development of breast cancer, as well as explore the potential therapeutic application of various isoflavones as complementary agents for breast cancer management. Materials and Methods Analysis of The Cancer Genome Atlas (TCGA) RNA-Seq and protein expression data at the Human Protein Atlas was performed for the identification of proteins. Furthermore, selected proteins were used for molecular docking and dynamics against various isoflavone derivatives. In addition, pharmacokinetic activity was performed for the isoflavone derivatives. Results Molecular docking exhibited the most potent binding energy of −9.6 kcal/mol for the CRMP2-genistin complex, closely followed by the HER2-daidzin complex with a binding energy of −9.4 kcal/mol. Subsequent molecular dynamics simulations showed dynamic behavior, structural integrity, stability, and interaction stability of HER2 protein with ligand daidzin. According to ADMET data, most soy isoflavones satisfy the Lipinski, Pfizer, Ghose, and GoldenTriangle criteria, indicating drug-like properties. Immunotoxicity projections indicate daidzein has the least adverse effects, while in silico , cytotoxicity assays indicate minimal overall risk. Glycitin and daidzin have the lowest levels of cytotoxicity. According to the comprehensive ADMET profiles, soy-derived isoflavones can safely complement current breast cancer therapeutics. Conclusion Computational analysis revealed that these ligands had inhibitory potential against BC-related HER2 and CRMP2 proteins. These isoflavones could be used to develop nutraceuticals to ensure safe and effective breast cancer management.