Epigenetic therapy approaches in non-small cell lung cancer: Update and perspectives

Non-small cell lung cancer (NSCLC) still constitutes the most common cancer-related cause of death worldwide. All efforts to introduce suitable treatment options using chemotherapeutics or targeted therapies have, up to this point, failed to exhibit a substantial effect on the 5-year-survival rate. The involvement of epigenetic alterations in the evolution of different cancers has led to the development of epigenetics-based therapies, mainly targeting DNA methyltransferases (DNMTs) and histone-modifying enzymes. So far, their greatest success stories have been registered in hematologic neoplasias. As the effects of epigenetic single agent treatment of solid tumors have been limited, the investigative focus now lies on combination therapies of epigenetically active agents with conventional chemotherapy, immunotherapy, or kinase inhibitors. This review includes a short overview of the most important preclinical approaches as well as an extensive discussion of clinical trials using epigenetic combination therapies in NSCLC, including ongoing trials. Thus, we are providing an overview of what lies ahead in the field of epigenetic combinatory therapies of NSCLC in the coming years.     

Variability in APOE genotype status in human-derived cell lines: a cause for concern in cell culture studies?

Although cell culture studies have provided landmark discoveries in the basic and applied life sciences, it is often under-appreciated that cells grown in culture are prone to generating artifacts. Here, we introduce the genotype status (exemplified by apolipoprotein E) of human-derived cells as a further important parameter that requires attention in cell culture experiments. Epidemiological and clinical studies indicate that variations from the main apolipoprotein E3/E3 genotype might alter the risk of developing chronic diseases, especially neurodegeneration, cardiovascular disease, and cancer. Whereas the apolipoprotein E allele distribution in human populations is well characterized, the apolipoprotein E genotype of human-derived cell lines is only rarely considered in interpreting cell culture data. However, we find that primary and immortalized human cell lines show substantial variation in their apolipoprotein E genotype status. We argue that the apolipoprotein E genotype status and corresponding gene expression level of human-derived cell lines should be considered to better avoid (or at least account for) inconsistencies in cell culture studies when different cell lines of the same tissue or organ are used and before extrapolating cell culture data to human physiology in health and disease.