Current perspectives on the use of miRNA as a biomarker for EGFR-targeted therapy for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the leading cause of death from cancer in the world. Currently, a large number of research studies are conducted to develop and implement new treatment strategies. Intensive efforts are also made to improve the robustness of modern molecular diagnostics to identify more precisely the specific genetic and epigenetic cancer features (predictive biomarkers) and to adjust the most effective treatment options for individual patients (personalized therapy). The so-called targeted therapy based on using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is nowadays the most widely chosen form of personalized treatment in advanced NSCLC. Favorable response to treatment with EGFR TKIs depends on the presence of somatic mutations in EGFR gene, detectable in lung cancer tissue. The resistance to EGFR TKIs acquired by most patients during the treatment is the main obstacle in overcome in targeted therapy of NSCLC. At present, epi-/genome of lung cancer is intensively screened using high-throughput techniques (e.g. microarrays, Next-Generation Sequencing) to select novel epi-/genetic biomarkers that could be used as predictors of the targeted treatment outcome, apart from single gene alterations. A better understanding of epigenetic mechanisms regulating either the sensitivity or the resistance of NSCLC cells to EGFR TKIs, through activity of small, non-coding miRNA (microRNA) molecules, may become a breakthrough in targeted therapy of lung cancer. During carcinogenesis, miRNAs exhibit their dual regulatory function: they promote cancer development as oncogenes or act as tumor suppressors. From a clinical point of view, such a dual regulatory function of microRNAs might significantly impact the further development of targeted therapies. Moreover, stable forms of tumor-related miRNA are detected not only in tumor tissue, but also in body fluids of NSCLC patients, particularly in their peripheral blood. This finding provides new options of minimally invasive cancer diagnosis and monitoring of treatment effectiveness over time.