MicroRNAs and Drug Resistance in Non-Small Cell Lung Cancer: Where Are We Now and Where Are We Going

SIMPLE SUMMARY: The problem of drug resistance represents a major challenge for the cure of non-small cell lung cancer. Tumor cells can be intrinsically resistant to drugs or they can become resistant during the treatment as a result of several adaptive responses. However, molecular mechanisms at the basis of drug resistance are not fully understood. MicroRNAs are small non-coding RNA that regulate gene expression and play critical functions in many cellular processes. Recently, the study of microRNAs has provided evidence about their role in the regulation of molecular mechanisms at the basis of drug resistance. Here we summarize the available knowledge about the role of miRNAs in the resistance to drugs that are currently used to treat non-small cell lung cancer and we critically discuss the experimental approaches on the basis of this evidence. ABSTRACT: Lung cancer is the leading cause of cancer-related mortality in the world. The development of drug resistance represents a major challenge for the clinical management of patients. In the last years, microRNAs have emerged as critical modulators of anticancer therapy response. Here, we make a critical appraisal of the literature available on the role of miRNAs in the regulation of drug resistance in non-small cell lung cancer (NSCLC). We performed a comprehensive annotation of miRNAs expression profiles in chemoresistant versus sensitive NSCLC, of the drug resistance mechanisms tuned up by miRNAs, and of the relative experimental evidence in support of these. Furthermore, we described the pros and cons of experimental approaches used to investigate miRNAs in the context of therapeutic resistance, to highlight potential limitations which should be overcome to translate experimental evidence into practice ultimately improving NSCLC therapy.