Abstract

Liquid biopsies are emerging as a patient-friendly approach for estimating biomarkers to predict treatment outcome and overall survival. Detection and characterization of circulating tumor cells (CTCs) is a promising biomarker and its application for non-small cell lung cancer (NSCLC) is currently under investigation. The FDA approved CellSearch system is used as the standard test. The most challenging hurdle in this and other techniques is to discern the CTCs from the background noise of normal blood cells. In the CellSearch system, lysis of erythrocytes, separating leukocytes with anti-CD antibodies, and immunomagnetic enrichment of cancer cells from blood samples expressing membranous epithelial cell adhesion molecule (EpCAM) protein is used. The relevant detection rate using CellSearch for prognosis is set by the developer on >2 (for metastatic colorectal cancer) or >4 CTCs (for metastatic breast and prostate cancer) per 7.5 mL blood sample. Clinical use of the CellSearch system is currently limited in NSCLC because it fails to detect CTCs at an acceptable rate and at a sufficient high yield. Extrapolation of CTC frequency distribution in 7.5 mL of blood from patients with metastatic breast, colon and prostate cancer showed that probably all these patients had CTCs in circulation, but the sample volume was not sufficient to detect them in all patients. Therefore, novel methods for the detection of CTCs are being studied.

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