Oxidative Stress and Nrf2 Signaling Role in Oral Squamous Cell Carcinoma: A Double‐Edged Sword
Ashraf Ullah Khan, Adnan Khan, Bushra Shal, Salman Khan, Sarah Sarwar, Jamshid Ullah, Amin Ullah, Kannan RR RengasamyABSTRACT
Background
Oxidative stress has a significant role in the origination and progression of oral squamous cell carcinoma (OSCC) by interrupting cellular redox homeostasis and gene regulation. The nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathway is a major regulator of antioxidant defense, activating cytoprotective genes under stress conditions.
Aim
The study highlight the dual role of the Kelch‐like ECH‐associated protein‐1 (Keap1)/Nrf2 signaling pathway in the development, progression, and therapeutic resistance of OSCC.
Methodology
Literature was conducted to evaluate the role of oxidative stress and Keap1/Nrf2 signaling in OSCC.
Results
Nrf2 protects normal cells from oxidative damage, its persistent activation in cancer cells promotes tumor progression, metabolic reprogramming, and resistance to chemotherapy and radiotherapy. Dysregulation of the Keap1/Nrf2 axis enhances cancer cell survival and contributes to radioresistance in OSCC. However, Nrf2 displays a dual function as both a tumor suppressor and promoter.
Conclusion
The Keap1/Nrf2 signaling pathway plays a key role in OSCC pathogenesis and treatment resistance. Targeting the Keap1/Nrf2 signaling pathway may provide a promising therapeutic strategy to overcome treatment resistance in OSCC.