Abstract
The use of targeted agents and immunotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC) has made it mandatory to characterize tumor tissue for patient selection. Moreover, the development of agents that are active against specific resistance mechanisms arising during treatment make it equally important to characterize the tumor tissue at progression by performing tissue re-biopsy. Given that tumor tissue is not always available for molecular characterization due to the paucity of diagnostic specimens or problems relating to the carrying out of invasive procedures, the use of liquid biopsy represents a valid approach to overcoming these difficulties. The most common material used for liquid biopsy in this setting is plasma-derived cell free DNA (cfDNA), which originates from cells undergoing apoptosis or necrosis. However, other sources of tumor material can be considered, such as extracellular vesicle (EV)-derived nucleic acids, which are actively secreted from living cells and closely correspond to tumor dynamics. In this review, we discuss the role of liquid biopsy in the therapeutic management of NSCLC with particular regard to targeted therapy and immunotherapy, and analyze the pros and cons of the different types of samples used in this context.
Highlights
The use of non-invasive methods to characterize tumors is a valuable tool for the management and assessment of cancer patients, e.g., at diagnosis, for the prediction of prognosis and response to therapy, and in the monitoring of response to treatment
The detection of programmed death-ligand 1 (PD-L1) protein in circulating tumor cells (CTCs) can be used to select patients who are more likely to respond to anti-PD-1/PD-L1 treatment, as immunofluorescence has shown that PD-L1 is expressed, together with the epithelial cell adhesion molecule (EpCAM), in over 80% of CTCs derived from metastatic lung cancer [101]
Since cell free DNA (cfDNA)-based assays are relatively low in complexity, in terms of purification and analysis, they are currently used in the clinical practice of non-small-cell lung cancer (NSCLC), and are considered the gold standard for defining the tumor mutational status and predicting treatment response by liquid biopsy
Summary
The use of non-invasive methods to characterize tumors is a valuable tool for the management and assessment of cancer patients, e.g., at diagnosis, for the prediction of prognosis and response to therapy, and in the monitoring of response to treatment. The introduction of targeted therapy into clinical practice has made it mandatory to characterize tumor tissue for patient selection, increasing the need for biological material for molecular analysis. In patients with advanced non-small-cell lung cancer (NSCLC) for whom diagnosis is normally made on small biopsies or cytology specimens, the frequent paucity of available tumor tissue is a serious problem. Molecular analysis of liquid biopsy normally takes less time than that of tumor tissue, which involves several steps and evaluations performed by a pathologist, with a consequent lengthening of the turnaround time. All these mechanisms of pharmacological resistance are potentially detectable via liquid biopsy
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