Liquid Biopsies in Lung Cancer

Simple Summary Liquid biopsy has recently been introduced as a novel method in cancer diagnostics. It is less invasive for patients than conventional tissue biopsies, as the assay material is drawn from peripheral blood. The detected DNA fragments, as well as the cells and extracellular vesicles, can be used as biomarkers for cancer. Not all biomarkers are equally reliable in cancer diagnostics. In this review, we give an overview of the lung cancer biomarkers identified in liquid biopsy assays and discuss the differences, current applications, and future perspectives of liquid biopsies in lung cancer. As lung cancer has the highest cancer-specific mortality rates worldwide, there is an urgent need for new therapeutic and diagnostic approaches to detect early-stage tumors and to monitor their response to the therapy. In addition to the well-established tissue biopsy analysis, liquid-biopsy-based assays may evolve as an important diagnostic tool. The analysis of circulating tumor DNA (ctDNA) is the most established method, followed by other methods such as the analysis of circulating tumor cells (CTCs), microRNAs (miRNAs), and extracellular vesicles (EVs). Both PCR- and NGS-based assays are used for the mutational assessment of lung cancer, including the most frequent driver mutations. However, ctDNA analysis might also play a role in monitoring the efficacy of immunotherapy and its recent accomplishments in the landscape of state-of-the-art lung cancer therapy. Despite the promising aspects of liquid-biopsy-based assays, there are some limitations regarding their sensitivity (risk of false-negative results) and specificity (interpretation of false-positive results). Hence, further studies are needed to evaluate the usefulness of liquid biopsies for lung cancer. Liquid-biopsy-based assays might be integrated into the diagnostic guidelines for lung cancer as a tool to complement conventional tissue sampling.