Abstract
Targeted molecular therapies have significantly improved the therapeutic management of advanced lung cancer. The possibility of detecting lung cancer at an early stage is surely an important event in order to improve patient survival. Liquid biopsy has recently demonstrated its clinical utility in advanced non-small cell lung cancer (NSCLC) as a possible alternative to tissue biopsy for non-invasive evaluation of specific genomic alterations, thus providing prognostic and predictive information when the tissue is difficult to find or the material is not sufficient for the numerous investigations to be carried out. Several biosources from liquid biopsy, including free circulating tumor DNA (ctDNA) and RNA (ctRNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs), have been extensively studied for their potential role in the diagnosis of lung cancer. This chapter proposes an overview of the circulating biomarkers assessed for the detention and monitoring of disease evolution with a particular focus on cell-free DNA, on the techniques developed to perform the evaluation and on the results of the most recent studies. The text will analyze in greater depth the liquid biopsy applied to the clinical practice of the management of NSCLC.
Highlights
In the era of precision medicine, the management of cancer patients has dramatically changed
The cf./ circulating tumor DNA (ctDNA) ratio can depends on the time of sample collection and clinical condition of the patient and is influenced by total tumor burden, location and extent of metastases, proliferation rate, apoptotic potential and genome instability [14]. ctDNA can enter the bloodstream through two different mechanisms: by a passive mechanism derived from apoptosis and necrosis or by an active mechanism derived from a spontaneous release of DNA fragment from primary tumor tissues or from circulating tumor cells or tumor-associated macrophages [15, 16]
Is tissue still the issue? One of the key questions facing oncologists today is whether ctDNA can replace biopsy or ribiopsy in clinical practice
Summary
In the era of precision medicine, the management of cancer patients has dramatically changed. Even in high expertise centers, the percentage of inadequate molecular results, in particular when small tissue samples are adopted, may be significant [6] In this setting, and in order to avoid to leave patients behind, liquid biopsy represents a valid option as a rapid, noninvasive and accurate clinical option. Several biosources from liquid biopsy, including free circulating DNA (cfDNA) and RNA (cfRNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs), can be isolated While each of these modalities has the potential to provide new diagnostic information and their exploration is highly encouraged, ctDNA certainly represents the most mature example of the survey on liquid biopsy in clinical practice for lung cancer patients. We will carefully analyze each step of the pre-analytical management of liquid biopsy specimen, (sample collection, ctDNA extraction, and molecular analysis) and the advantages and disadvantages found in the use of liquid biopsy respect the adoption of gold standard tissue sample in the context of clinical practice
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