Structural pharmacogenomics of drug-associated SNPs in oral squamous cell carcinoma.

Introduction: Pharmacogenomics enables the interpretation of how genetic variation influences drug response, offering a route toward precision oncology. Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy characterized by marked inter-individual variability in response to chemotherapy and radiotherapy, particularly in South Asian populations. However, the mechanism through which OSCC-associated genetic variants alter protein structure and drug interactions remains poorly understood. Methods: To address this, we integrated OSCC-specific variants from a Southern Indian patient cohort with pharmacogenomic annotations from ClinPGx. First, OSCC variants were mapped to drug-associated single-nucleotide proteins, yielding 22 protein-altering variants. Second, structural availability and functional relevance were used to prioritize eight variants for detailed analysis. Third, homology modeling and molecular docking were applied to evaluate how these variants influence protein conformation and drug binding. Result: This multistep pipeline identified variants in Conclusion: These findings demonstrate how pharmacogenomics-guided structural analysis can reveal mechanistic links between OSCC-associated variants and therapeutic response. While our results are based on