Molecular Characterization of Circulating Tumor Cells: Holy Grail for Personalized Cancer Treatment?

The classic biopsy approach does not allowmonitoring of primary tumor evolution over time, and sampling of metastatic sites is not always possible for practical rea-sons. Through a simple blood draw, circulating tumor cells (CTCs)2 can serve as a “liquid biopsy ” and an early marker of response to systemic therapy, whereas mo-lecular characterization ofCTCs has strong potential to be translated to individualized targeted treatments (1–3). It has been shown through numerous studies that CTC detection and enumeration in the blood of cancer patients is associated with poor outcome, and a number of clinical trials are now assessing their clinical importance (4). However, CTCs are very rare and make up a small minority of cells circulating in blood, so their molecular analysis beyond enumeration is technically very challenging (1, 2). Discovering the complete picture of CTC biology will enable the dream of precision medicine and personalized therapy to be realized, by facilitating the targeting of specific cell sub-types. This is not an easy task, since CTCs are not only rare but heterogeneous at the same time, even within the same patient (5, 6). In this issue of Clinical Chemistry, 2 different Eu-ropean groups present some very interesting data on the potential utility of CTCmolecular characterization in the clinic (7, 8). Although they use completely dif-ferent experimental approaches, and although they fo-cus on different cancer types, both groups show clearly that understanding CTC biology could be a key issue in favor of cancer patients. Neves et al. have developed a work flow to effi-ciently purify single CTCs from clinical samples cap-tured through the FDA-cleared CellSearch ™ system (7). This system is automated and widely used in clin-ical laboratories for CTC enumeration, since it gives clinically important information at the metastatic set-ting for breast, colorectal, and prostate cancer (9). However, the CellSearch system has some limitations because it is a closed system designed to detect and enumerate EpCAM/CK/CD45/DAPI CTCs (EpCAM epithelial cell adhesion molecule, C