Epigenetics in non-small cell lung cancer: from basics to therapeutics

Lung cancer is a cancer of the modern man and only few cases date before the 20th century. By the mid-twentieth century it had swept the world, due to increased worldwide tobacco consumption (1). Even after widespread awareness about smoking in the last 4–5 decades, the lung cancer incidence has only plateaued and in the developed world, it still accounts for approximately 25% of cancer-related deaths. Detection of lung cancer at an early stage leads to a better prognosis; the 5-year survival for localized lung and bronchus cancer is 54.8%, compared to 27.4% for regional, and 4.2% for widely disseminated disease (1). Lung cancers are classified into small cell and non-small cell lung cancers (NSCLC) and approximately 80% are comprise of NSCLCs, which are classified into adenocarcinoma (AdC), adenosquamous carcinoma, squamous cell carcinoma (SqCC), and large cell carcinoma based on tumor histology, with 80% of NSCLC being either AdC or SqCC (2,3). Based on the molecular pathogenesis patterns and histologic classification, AdCs are the most common type to show common recurrent genomic gains and losses, and somatic mutations. These driver mutations have been extensively studied in AdCs and the most common ones mutated are the epidermal growth factor receptor (EGFR), KRAS, and anaplastic lymphoma kinase (ALK) oncogenes (2,3)