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.
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