In Silico and Multi-Omics Exploration of EGFR-Targeting Hits Against Colon Cancer
DOI:
https://doi.org/10.64149/J.Carcinog.24.10s.471-484Keywords:
Colon cancer, Epidermal Growth Factor Receptor (EGFR), in silico technique, KEGG pathway, Encorafenib, ADMET propertiesAbstract
Background: Colon cancer is a serious global health concern caused by genetic variability and abnormal signaling pathways, such as the epidermal growth factor receptor (EGFR) axis. Although EGFR is a well-known therapeutic target in colorectal cancer, its expression pattern and function in colon cancer are context dependent.
Methods: This study used an integrated in silico technique that included transcriptome analysis, pathway enrichment, molecular docking, pharmacophore modeling, virtual screening, ADMET profiling, and molecular dynamics (MD) simulation to find and assess new small-molecule EGFR inhibitors.
Results: TCGA data showed downregulated EGFR expression in colon cancer tissues, with no significant patient survival association. KEGG pathway analysis revealed EGFR's central role in oncogenic pathways like PI3K-Akt and MAPK. Molecular docking identified Encorafenib as a strong EGFR binder, serving as a template for pharmacophore generation. Virtual screening of ZINC database compounds identified ZINC103239230 as a top hit. ZINC103239230, a promising candidate for further development, demonstrated favorable ADMET properties and formed a stable complex with EGFR in a 100 ns MD simulation, indicating its potential as a therapeutic target in colon cancer. This strategy holds promises for accelerating drug development, reducing resistance, and promoting oncology customized treatment.
