Genomic Instability And Dna Damage Response In Oral Squamous Cell Carcinoma: Molecular Mechanisms, Tumor Evolution, And Therapeutic Vulnerabilities
DOI:
https://doi.org/10.64252/r2a1jr45Keywords:
Chromosomal Aberrations, Epigenetic Alterations, Homologous Recombination Deficiency, Microsatellite Instability, Oxidative Stress, Parp Inhibitors.Abstract
This review comprehensively examined the molecular mechanisms of genomic instability and DNA damage response (DDR) in oral squamous cell carcinoma (OSCC), emphasizing tumor evolution and therapeutic vulnerabilities. It highlighted how genotoxic agents induced DNA strand breaks, microsatellite instability, and chromosomal aberrations, with key mutations identified in TP53, CDKN2A, and NOTCH1. The DDR network involving ATR, ATM, PARP, and BRCA proteins was outlined, revealing its role in maintaining genomic integrity and its disruption contributing to OSCC progression. The review discussed oxidative stress and ROS-mediated oncogenic pathways, along with epigenetic alterations, cGAS/STING signaling, and immune evasion strategies. Biomarkers like homologous recombination deficiency (HRD) scores, mutation signatures, and extracellular markers were identified as diagnostic and prognostic tools. Lastly, therapeutic targets including PARP, ATR, CHK1, and WEE1 inhibitors were analyzed, underscoring their clinical potential in sensitizing OSCC to chemoradiotherapy and immunotherapy.
