Abstract
Lung cancer is one of the highest incidence cancer types worldwide and one with the lowest 5-year survival rate of all cancer types. Despite recent insights into lung cancer pathobiology, including novel biomarker-targeted therapies and immunotherapies, most of lung patients are diagnosed at late stages with limited and ineffective treatments. Therefore, more approaches are needed to eradicate lung cancer. In the last years, small extracellular vesicles (EVs) secreted by tumor cells have been gaining relevance. These intercellular signal mediators, called exosomes, contain a huge range of biological elements, including lipids, nucleic acids and miRNAs, among others, that carry relevant information. The role of exosomes in cancer progression is dependent on cancer type, molecular characteristics and stage. MicroRNAs molecules are a big part of the content of exosomes cargo and probably the most studied ones. Due to the regulatory role in gene expression, miRNAs may provide information of the molecular characteristics of the tumor and be also able to reprogram distant target cells. Exosomal miRNAs can modulate different biological processes in cancer such as growth, progression, invasion, angiogenesis, metastasis and drug resistance; playing a critical role in modifying the microenvironment of non-small cell lung cancer (NSCLC). Therefore, they can act by regulating tumor resistance and also be useful to monitoring the response/relapse to targeted therapies. In this work, we summarize the relevant advances on the potential role of exosomal miRNAs in NSCLC pathobiogenesis, highlighting the clinical utility of exosomal microRNAs as biomarkers for the NSCLC diagnosis, prognosis, drug resistance and therapeutic strategies.