Liquid Biopsy in NSCLC: An Investigation with Multiple Clinical Implications

Abstract

Tissue biopsy is essential for NSCLC diagnosis and treatment management. Over the past decades, liquid biopsy has proven to be a powerful tool in clinical oncology, isolating tumor-derived entities from the blood. Liquid biopsy permits several advantages over tissue biopsy: it is non-invasive, and it should provide a better view of tumor heterogeneity, gene alterations, and clonal evolution. Consequentially, liquid biopsy has gained attention as a cancer biomarker tool, with growing clinical applications in NSCLC. In the era of precision medicine based on molecular typing, non-invasive genotyping methods became increasingly important due to the great number of oncogene drivers and the small tissue specimen often available. In our work, we comprehensively reviewed established and emerging applications of liquid biopsy in NSCLC. We made an excursus on laboratory analysis methods and the applications of liquid biopsy either in early or metastatic NSCLC disease settings. We deeply reviewed current data and future perspectives regarding screening, minimal residual disease, micrometastasis detection, and their implication in adjuvant and neoadjuvant therapy management. Moreover, we reviewed liquid biopsy diagnostic utility in the absence of tissue biopsy and its role in monitoring treatment response and emerging resistance in metastatic NSCLC treated with target therapy and immuno-therapy.

A comparative study of circulating tumor cell isolation and enumeration technologies in lung cancer

“…Currently the assessment of CTCs has not translated into the routine clinical management of NSCLC patients. Reproducibility and sensitivity remain a challenge as do issues with manual processes and low recovery rates [17][18][19][20]. Here we evaluate the recovery rates of 5 different CTC isolation systems including: the CellMag™ system which uses a manual immuno-magnetic (ferrofluid technology) enrichment of epithelial cells using the epithelial cellular adhesion molecule (EpCAM) and is based on the same technology as the CellSearch®; EasySep™ targets cells for either removal (negative selection via CD45 depletion) or positive selection using antibody complexes directed to specific cell surface antigens; RosetteSep™ is an immunodensity procedure that isolates unlabeled CTCs using an antibody cocktail to deplete monocytes along with erythrocytes from whole blood; Parsortix® PR1 enables the separation and capture of cells present in blood based on their size and deformability [17] and the Parsortix® PX+ which is ANGLE plc's next generation system currently undergoing beta-testing and utilizes the same isolation method as the PR1.…”