ORIGINAL RESEARCH article
Front. Genet.
Sec. Pharmacogenetics and Pharmacogenomics
This article is part of the Research TopicClinical Adoption of Pharmacogenetics: Insights from Practice and Pioneering ResearchView all articles
Structural Pharmacogenomics of Drug-Associated SNPs in Oral Squamous Cell Carcinoma
Provisionally accepted
- Yenepoya Research Centre, Yenepoya University, Mangalore, India
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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 with marked inter-individual variability in response to chemotherapy and radiotherapy, particularly in South Asian populations. However, how 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 SNPs, 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 multi-step pipeline identified variants in FLT3, ATM, MUTYH, XRCC1, XPC, and MSH3 that affect DNA repair, signaling, and drug interaction interfaces. The highly prevalent FLT3 T227M (rs1933437) variant was predicted to alter receptor dimerization and potentially modulate sunitinib binding. The MUTYH Q310H (rs3219489) variant, located near a zinc-binding motif in the interdomain connector, was predicted to perturb metal coordination and enzyme architecture, suggesting impaired base-excision repair. 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 in-silico modelling, they provide a biologically grounded framework for prioritizing variants for experimental validation and for advancing population-specific precision oncology in OSCC.
Keywords: chemoresistance, DNA repair genes, Oral Squamous CellCarcinoma (OSCC), personalized medicine, pharmacogenomics, Single nucleotide polymorphisms (SNPs)
Received: 15 Jul 2025; Accepted: 12 Jan 2026.
Copyright: © 2026 Sunil, Kumar KC, AI, Gupta and Das. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ranajit Das
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.