Collagen Type 1 Alpha 1 Chain as a Potential Therapeutic Target Shared Among Subtypes of Head and Neck Squamous Cell Carcinoma: Quantum Chemical Modeling of Bleomycin for Anticancer Drug Repurposing

Abstract

Head and neck squamous cell carcinoma (HNSCC) displays significant molecular heterogeneity, which hinders effective and safe treatments and clinical outcomes. This predicament also points to the need for an individually tailored personalized/precision medicine approach in HNSCC that includes the oral, hypopharyngeal, nasopharyngeal, and laryngeal subtypes. This study, with the overarching aim of personalized/precision medicine, attempted to identify (1) a molecular target shared by the HNSCC subtypes and (2) screen for potential anticancer drugs for repurposing that may work across the HNSCC subtypes. The National Center for Biotechnology Information—Gene Expression Omnibus database was used to select the datasets (GSE127165, GSE2379, GSE37991, and GSE12452) for the analyses of differentially expressed genes in HNSCC subtypes. Our transcriptome analyses of the HNSCC subtypes revealed 305 upregulated genes. Subsequently, protein network construction with 305 genes showed three closely interconnected high-risk HNSCC prognostic clusters. Importantly, COL1A1 was identified as the pivotal target regulating the pathogenic cluster protein implicated in cancer pathways. Molecular docking with 1040 anticancer drugs identified bleomycin as a potential candidate, exhibiting a binding affinity of −12.425 kcal/mol and a favorable binding free energy of −92.05 kcal/mol. The dynamic simulations confirmed the stability of the system, with stable interactions over 200 ns. Quantum calculations provided insights into bleomycin’s chemical and electronic properties, revealing crucial interactions with COL1A1. In conclusion, our study proposes COL1A1 as a promising potential therapeutic target among HNSCC subtypes, with bleomycin demonstrating notable repurposing potential for HNSCC.