Epigenetic Therapy as a Potential Approach for Targeting Oxidative Stress-Induced Non-small-Cell Lung Cancer

Lung cancer is considered as the leading cause of cancer-related deaths globally. Etiology of lung cancer include smoking, genetic factor, age, gender, ethnicity, race, diet, obesity, infections, environmental air pollution, occupational exposure, and chronic respiratory diseases. Oxidative stress mediated by cigarette smoking facilitates DNA mutation, the proliferation of lung epithelial cells, and as a result of oncogenic activation leading to the progression of lung cancer. Cigarette smoke also induces microRNA-mediated stress response, genetic expression, and apoptosis. Epigenetic regulations such as chromatin remodeling, DNA methylation, chromatin modifications, microRNA modulations, and histone modification are associated with carcinogenesis. The precise identification of genetic mutations that primarily drive tumor initiation and/or disease progression could lead to the development of targeted treatments that may improve the disease outcomes along with increasing life expectancy for patients with lung cancer. Histone deacetylase inhibitors (HDACi) are emerging as a potential epigenetic therapy for non-small-cell lung cancer (NSCLC). HDACi such as vorinostat, panobinostat, istodax, or entinostat may hold the potential to restore the downstream pathway involved in the lung cancer pathogenesis. Furthermore, HDACi has also been used in NSCLC clinical trials, either as monotherapy or as an adjuvant with radiotherapy or chemotherapy. HDACi as an adjuvant exerts potent antitumor efficacy in treating NSCLC. A combination of vorinostat, carboplatin, and paclitaxel has high efficacy in treating advanced NSCLC. In this review, we have highlighted the role of oxidative stress-mediated epigenetic changes leading to lung cancer progression and the potential of epigenetic therapy for lung cancer.