Combining structure-based and 3D QSAR pharmacophore models to discover diverse ligands against EGFR in oral cancer.

Epidermal growth factor receptor-tyrosine kinase (EGFR-TK) is a well-known hallmark of oral and oropharyngeal cancers, as its overexpression leads to poor prognosis and malignancy. The activating EGFR mutations (particularly T790M and L858R double mutant) are a major challenge causing drug resistance, especially in the treatment of oral cancers. This paper is an effort to exploit both structure-based and ligand-based pharmacophore modeling to discover EGFR-TK inhibitors, which show inhibition of proliferation of erlotinib-resistant FaDu and Cal27 oral cancer cells. Interestingly, the hit compound also showed an effect on the downstream glucose and lactate metabolism pathways. The results indicate the potential of to be developed as an EGFR-based metabolic inhibitor for oral cancer treatment.