Abstract

Simple Summary This study systematically investigates the shared molecular mechanisms through which prevalent endocrine-disrupting chemicals (EDCs) may contribute to the pathogenesis of four major urogenital cancers: bladder cancer (BLCA), renal cell carcinoma (RCC), prostate adenocarcinoma (PRAD), and testicular germ cell tumor (TGCT). Using an integrated computational framework combining network toxicology, protein–protein interaction analysis, molecular docking, and dynamics simulations, the research identifies common hub protein targets linking exposure to 12 EDCs with tumor progression in a cancer-type-specific manner. Key shared targets include EGFR and CASP3 in BLCA, EGFR and CASP9 in RCC, CASP3, ESR1, and EGFR in PRAD, and KIT in TGCT. The benzo[a]pyrene (BaP)–CASP9 interaction, predicted to have high binding affinity, was selected for experimental validation. Results show that chronic exposure to an environmentally relevant concentration of BaP post-transcriptionally increases CASP9 protein stability in multiple urogenital cancer cell lines. These findings delineate converging molecular pathways for EDCs across different urogenital malignancies and highlight potential biomarkers and therapeutic targets for environmentally associated cancers.