Molecular biology of lung cancer

Recent advances in biotechnology have made it possible to explore the molecular pathogenesis of human lung cancer. Since the 1980s, various alterations, including mutations in the P53 and KRAS genes, allelic alterations like loss of heterozygosity, and DNA methylation of tumor-related genes have been extensively studied. In 2004, epidermal growth factor receptor (EGFR) gene mutation was discovered in non-small cell lung cancer (NSCLC) as an alteration that causes oncogene addiction. EGFR mutation is also significantly associated with sensitivity to EGFR-tyrosine kinase inhibitors (TKI), which has encouraged intensive studies not only on the EGFR gene but also on the EGFR family and its downstream genes. Furthermore, EML4-ALK fusion genes have been found in NSCLC, and as in EGFR-TKIs, an ALK inhibitor shows a drastic response in NSCLC with the EML4-ALK fusion gene. These discoveries demonstrate that basic research can develop novel therapeutic strategies to improve the prognosis of lung cancer. In this review, we summarize the crucial findings of molecular pathogenesis in lung cancer, especially NSCLC, and show the possible future direction of related molecular biological research.