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Circulating tumor cell isolation: a marathon race worth running.

It took almost 150 years after the first report on the presence of circulating tumor cells (CTCs)2 by Thomas Ashworth in 1869 (1) to reach the point at which their detection and molecular characterization is one of the hottest fields in cancer research (2). The clinical significance of CTCs has been evaluated in many types of solid cancers, and the Food and Drug Administration (FDA) cleared the testing of CTCs in metastatic breast, colorectal, and prostate cancer almost a decade ago (3).

In contrast to tumor biopsies, peripheral blood samples can be frequently and sequentially obtained for CTC isolation and downstream analysis. The noninvasive isolation of CTCs from peripheral blood and their further downstream molecular characterization at the protein, DNA, and RNA levels could now serve as a “liquid biopsy” approach, eventually offering additional information and, even more, a serious advantage over the conventional and well-established tumor biopsy approach (4, 5). Cell-free DNA circulating in plasma or serum of cancer patients has also been recently proposed as an alternative to the CTC liquid biopsy approach (6). By the use of extremely powerful and highly sensitive detection techniques, the presence of specific mutations in the plasma of patients with cancer could give valuable information concerning responses to specific molecular targeted therapies (7). However, there is a substantial difference between these two approaches; CTCs are viable cells that circulate in blood, and understanding their biology in a holistic way could give valuable information on metastatic spread, clarify their connection to cancer stem cells, and reveal active and possible targetable signaling networks. Cell-free DNA could give specific information as a circulating biomarker for the presence or absence of specific alterations indicating therapy response.

The …