Utilizing circulating tumor cells: challenges and pitfalls

Circulating tumor cells (CTC) detected in the blood of cancer patients could be used for risk-stratification, molecular subclassification and as an intermediate end-point in therapeutic efficacy studies. Most studies to date have focused on enumeration of CTC in advanced cancer patients but further development of CTC evaluation technologies could allow expansion into early disease, monitoring of treatment response, and selection of patients for targeted therapies based on a CTC derived signature. This review discusses the challenges faced in achieving these goals, including the potential absence of CTC in patients with no blood-borne metastases, CTC intra-patient molecular heterogeneity, ex vivo loss of CTC viability, and the biological differences between CTC and metastatic tissue.