DNA repair mechanisms and their therapeutic implications in oral cancer

Abstract

Oral cancer, especially oral squamous cell carcinoma (OSCC), remains a significant global health problem due to poor prognosis and high mortality despite advances in conventional treatment. DNA repair mechanisms are essential for maintaining genomic stability and influencing both oral cancer development and treatment response. In this review, we discuss the current understanding of DNA repair pathways in oral cancer, their clinical significance, and potential therapeutic applications. We systematically reviewed the literature and analyzed studies on DNA repair mechanisms, their dysregulation in oral cancer, and emerging targeted therapies. Key findings indicate that DNA repair defects are prevalent in OSCC, contributing to genomic instability and resistance to DNA-damaging therapies. Tobacco, alcohol, and chronic inflammation are major carcinogenic factors that cause widespread DNA damage and often overwhelm cellular repair systems. Epigenetic modifications further exacerbate repair failure, affecting tumor progression and treatment outcomes. Recent advances demonstrate the efficacy of DNA repair-targeted strategies, especially poly ADP-ribose polymerase (PARP) inhibitors, which hold promise for homologous recombination-deficient tumors. Furthermore, DNA repair status has emerged as a valuable biomarker for prognostic applications and can guide patient selection for precision medicine approaches. However, resistance mechanisms to DNA repair inhibitors, such as pathway rewiring and compensatory repair activation, remain a major challenge. Future studies should focus on integrating DNA repair assessment into clinical decision-making, refining biomarker strategies, and developing rational combination therapies to overcome resistance. A deeper understanding of DNA repair dynamics in oral cancer may lead to more effective and personalized treatment strategies, ultimately improving patient outcomes.