Technical challenges in the isolation and analysis of circulating tumor cells

Increasing evidence suggests that cancer cells display dynamic molecular changes in response to systemic therapy. Circulating tumor cells (CTCs) in the peripheral blood represent a readily available source of cancer cells with which to measure this dynamic process. To date, a large number of strategies to isolate and characterize CTCs have been described. These techniques, however, each have unique limitations in their ability to sensitively and specifically detect these rare cells. In this review we focus on the technical limitations and pitfalls of the most common CTC isolation and detection strategies. Additionally, we emphasize the difficulties in correctly classifying rare cells as CTCs using common biomarkers. As for assays developed in the future, the first step must be a uniform and clear definition of the criteria for assigning an object as a CTC based on disease-specific biomarkers.