Clinical Implications of Epigenetic Alterations in Lung Cancer

Lung cancer cells and cell lines have been extensively studied for epigenetic alterations including global and gene-specific DNA hypermethylation, aberrant histone acetylation and methylation, and resultant gene expression changes. These epigenetic disturbances have provided rational targets for preclinical and clinical development including epigenetically active drugs. While single agent histone deacetylase inhibitor treatment has only modest activity in lung cancer, the combination with other drugs such as the DNA hypermethylating agent decitabine shows promise particularly in tumor cell reprogramming. In this regard, modulation of cancer/testis antigens provides a novel approach of rendering lung cancer cells more immunogenic, e.g., to active immunotherapy. In addition, the combination of epigenetic drugs with standard chemotherapy or tyrosine kinase inhibitors offers novel, exciting venues to more effectively treat these diseases.