Liquid biopsies in lung cancer—a narrative review

Abstract

Background and Objective: The use of liquid biopsies to detect not only genetic and epigenetic alterations in circulating DNA but also to identify circulating non-coding RNAs (ncRNAs) is a promising tool for diagnosis, prognosis and prediction of therapy outcome of cancer patients. The objective of the narrative review is to describe the genetically and epigenetically altered circulating DNA as well as the identification of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in both peripheral blood and other bodily fluids, but also in exosomes as potential biomarkers for lung cancer identification. Methods: In the following article we summarized important aspects from the studies listed in database PubMed using keywords “circulating, cell-free DNA, RNA, ncRNAs, microRNAs, lncRNAs, circRNAs, exosomes” and “lung cancer” from 1985–2022. A total of 450 articles were considered and 149 relevant articles were included in the review. Key Content and Findings: In lung cancer patients, new molecular technologies of circulating tumor DNA and miRNAs have been shown to increase the odds of finding the occurrence of targetable mutations in this deadliest malignancy worldwide. The clinical application of relevant non-invasive DNA biomarkers, such as EGFR, ALK, ROS-1, MET and PD-L1, has been investigated for introduction into daily clinical practice. Cell-free EGFR mutations have been approved in selecting patients for treatment with tyrosine kinase inhibitors and assays for their detection have already entered clinical practice. Conclusions: Although the application of (I) circulating miRNAs for the detection of lung cancer has not entered clinical practice, and (II) circulating DNA has only been exploited in some cases, their utility for diagnosis, prognosis, and prediction of different treatment strategies is promising. In particular, the consideration of exosomes containing these molecules is essential since they are important factors for the propagation of cancer.