Investigation of the Molecular Mechanisms of Paraoxonase‐2 Mediated Radiotherapy and Chemotherapy Resistance in Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is a common form of cancer, with 390,000 new cases estimated for 2022. OSCC has a poor prognosis, largely due to a high recurrence rate and resistance to therapy. Cancer cells develop resistance to standard therapy owing to various factors, such as genetic predispositions, alterations in the apoptotic pathway coupled with DNA repair pathways, drug efflux, and drug detoxification. This review is aimed at exploring the crucial role of paraoxonase 2 (PON2) in conferring resistance to chemotherapy and radiotherapy in OSCC cells. PON2, an antioxidant enzyme, protects cancer cells from the oxidative stress caused by these treatments. By influencing apoptotic pathways and DNA repair mechanisms, PON2 can reduce the effectiveness of therapy. This review is an attempt to explore the complex molecular mechanisms modulated by PON2, such as the mitigation of oxidative stress, enhancement of DNA repair, apoptosis regulation, drug efflux modulation, and drug detoxification, which decrease treatment efficacy.