Investigating new inhibitors with potential advantages for combating HER2-overexpressing head and neck squamous cancer cells; a practical and virtual screening study

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) are between most common cancer worldwide. Most HNSCC tumors are characterized by higher expression of human epidermal growth factor receptor 2 (HER2) that is related to resistance to chemotherapy and radiotherapy. Accordingly, HER2 has been proposed as a fair target for specific chemotherapy. Lapatinib as a potent inhibitor of the EGFR family were proposed for the treatment of HER2-positive HNSCC cases. In current study, at first step we used the crystal structure of HER1-lapatinib complex (PDB ID: 1XKK) to deeply investigate lapatinib interaction with HER1. Based on the HER1-lapatinib crystal structure and conserved structure of EGFR family, we made a confirmed coordination to survey HER2-lapatinib interactions. After investigation of lapatinib with HER1 and HER2 structures via docking approach, we evaluated lapatinib effect on HN5 cells as HER2-overxpressing HNSCC-originating cell line. At last, we used created 3D coordination to introduce other efficient and specific inhibitors for HER1 and HER2 based on virtual screening processing according on structural similarity to lapatinib. Also, Pharmacokinetic properties of indicated ligands were assessed by ADMET in silico modelling tool. Obtained results showed, in accordance with our obtained docking result while the presence of lapatinib could enhance the optimum effect of cisplatin on ablation of HN5 cells it could not empower the specific effect of cisplatin on HN5 cells when compared with normal HER2-expressing MCF-7 cells. Following, based on virtual screening process, we introduce agents with high and specific affinity for HER1 and HER2.