Chronic nicotine exposure affects programmed death-ligand 1 expression and sensitivity to epidermal growth factor receptor-tyrosine kinase inhibitor in lung cancer

Somatic mutation of the epidermal growth factor receptor (EGFR) gene is a major oncogenic driver in non-small cell lung cancer (NSCLC) (1). Patients with advanced NSCLC harboring EGFR mutation can receive EGFR-tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and afatinib with high response rates for first-line treatment (2). However, acquired resistance to EGFR-TKIs in metastatic setting is inevitable, although initial responses are dramatic. In addition, ~20–30% of patients have no good initial clinical response to EGFR-TKIs, although they harbor sensitizing EGFR mutations (3). These primary resistant mechanisms can be explained by de novo resistant mutation, suboptimal drug exposure, failure of apoptosis induction, and other somatic alterations on genes encoding components of major signaling pathways (4). After tumor progression, novel third-generation EGFR-TKIs such as osimertinib and olmutinib have been designed to overcome resistance due to T790M mutation (5,6). Other strategies to overcome different mechanisms are also under development (7,8)