Circulating Tumor Cells and Colorectal Cancer

Abstract

The significance of circulating tumor cells (CTCs) has been discussed for more than a century. The advent of modern technology has allowed for more reliable detection of CTCs, and recent studies have provided compelling evidence that CTCs predict clinical response in metastatic colorectal cancer (mCRC). Combination of CTC analysis with independent prognostic factors has demonstrated powerful synergy in some studies. The ability of CTCs to predict metastasis and therapy-specific response has high potential clinical utility, with early studies showing promising results in colorectal cancer (CRC). Reliable CTC detection has also allowed for examination of tumor cell dissemination during surgery, and there appears to be a heavy dependence on the approach chosen. This review discusses the evidence for CTC significance, with particular focus on detection methods, novel markers, and clinical outcomes in CRC. Numerous opportunities exist for preclinical, clinical, and translational studies to explore molecular determinants within CTCs, as well as the value of CTCs in directing targeted therapeutics.

Fig. 1

Circulating tumor cell (CTC) generation, identification, and detection. CTCs are shed from the primary tumor and intravasate by several possible mechanisms: direct shedding into existing blood vessels (A), mechanical disruption (eg, resection; [B]), or shedding into angiogenic capillaries (C). CTCs then travel through the bloodstream (D) and later extravasate at a potential site of metastasis (E). CTCs can be detected in peripheral blood by collection (F) using a variety of methods (G). Published markers for CTCs in colorectal cancer are listed (H). CellSearch is a registered trademark of Veridex LLC, Raritan, NJ. qRT-PCR, quantitative reverse transcriptase polymerase chain reaction