Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation, bypass signaling pathway activation and histological transformation. And the most common mechanism is T790M which accounts for approximately 50% of all subtypes. Many strategies have been explored to overcome the acquired resistance to EGFR TKI. Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones. While the combination of EGFR TKI and chemotherapy or other targeted agents has improved the survival benefit in EGFR TKI resistant patients, there are controversies within them. The next-generation EGFR TKI and immunotherapy represent two novel directions for overcoming acquired resistance and have achieved promising efficacy. Liquid biopsy provides surveillance of the EGFR mutation by disclosing the entire genetic landscape but tissue biopsy is still indispensable because of the considerable rate of false-negative plasma.

Influence of environmental static electric field on antioxidant enzymes activities in hepatocytes of mice.

With the increasing voltage of direct current transmission line, the intensity of the environmental static electric field has also increased. Thus, whether static electric fields cause biological injury is an important question. In this study, the effects of chronic exposure to environmental static electric fields on some antioxidant enzymes activities in the hepatocytes of mice were investigated. Male Institute of Cancer Research mice were exposed for 35 days to environmental static electric fields of different electric field intensities of 9.2-21.85 kV/m (experiment group I, EG-I), 2.3-15.4 kV/m (experiment group II, EG-II), and 0 kV/m (control group, CG). On days 7, 14, 21, and 35 of the exposure cycle, liver homogenates were obtained and the activities of antioxidant enzymes like superoxide dismutase, glutathione S-transferase, and glutathione peroxidase were determined, as well as the concentration of malonaldehyde. The results revealed a significant increase in superoxide dismutase activity in both EG-I and EG-II on the 7th (P < 0.05) and 35th days (P < 0.01) of the exposure cycle compared to that in the control group. However, the other test indices such as glutathione S-transferase, glutathione peroxidase, and malonaldehyde showed only minimal changes during the exposure cycle. These results revealed a weak relationship between the exposure to environmental static electric fields and hepatic oxidative stress in living organisms.