Liquid biopsy based on circulating tumor cells and estracellular vesicle mirnas for the relapse and death risk stratification in non-small cell lung cancer patients

Abstract

Lung cancer is the leading cause of cancer-related death in the world, being non-small cell carcinoma (NSCLC) the most common histological subtype, comprising 80% of all cases. Despite major breakthroughs in the diagnosis and treatment of this neoplasia, relapses are early developed and the survival rate remains still low, with a 5-year rate of ~18%(1). In early stages of NSCLC (I-IIIA), surgery is the mainstay of treatment and the most effective, with only little benefit from the addition of adjuvant platinum-based chemotherapy(2). On the other hand, most NSCLC patients are diagnosed at advanced stages, where survival rates are even lower, with a reported 5-year survival rate of 5%. In these patients, concomitant chemo-radiotherapy is the standard of care but progression is developed even earlier(3). The failure of the treatments might be caused by the complex heterogeneous and dynamic nature of tumors(4) and the molecular differences between adenocarcinomas and squamous cell carcinomas, that the traditional tissue biopsy might not reflex. Thus, new prognostic and predictive markers are need. Circulating tumor cells (CTCs), found in blood, has been associated with the metastatic process and postulated as potential prognostic factors in these patients. However, little is known about the release of heterogeneous subpopulations of CTCs that can be found in a single patients(5). miRNAs (miR), known as important regulators of cancer genes, can be selectively encapsulated into extracellular vesicles (EVs) by cancer cells, acting also as cancer biomarkers(6). EVs and the autophagy mechanisms play crucial roles in response to cellular stress for the consequent maintenance of cellular homeostasis and their crosstalk might represent therapeutic opportunities in NSCLC.