Circulating cancer cells and their clinical applications.

Minimal residual cancer is defined as “the presence of tumor cells that are not detectable by the current routine diagnostic procedures used for tumor staging in cancer patients after surgical removal of the primary tumor.” Data from European and North American groups have demonstrated the prognostic impact of disseminated tumor cells (DTCs) in the bone marrow of breast cancer patients. Circulating tumor cell (CTC) detection and enumeration in peripheral blood have been examined in prospective multicenter studies of metastatic breast, colorectal, and prostate cancers and have been associated with decreased progression-free and overall survival. An increasing number of clinical research studies are validating these observations and extending them to other cancers and to earlier disease stages. CTCs are highly heterogeneous, and their molecular characterization is important, not only to confirm their malignant origin but also to follow immunephenotypic changes with tumor progression and identify diagnostically and therapeutically relevant targets that will help stratify cancer patients for individualized therapies. The rarity of CTCs—and thus the very limited amount of available sample—presents a formidable analytical and technical challenge. Recent technical advances in CTC detection and characterization include reverse-transcription quantitative PCR (RTqPCR) methods, image-based approaches, and microfilter and microchip devices. CTCs represent a promising new diagnostic field for advanced-stage patients in that the sensitive CTC-detection platforms allow monitoring of disease and treatment efficacy. The development of single-cell technologies might allow profiling of these cells for the purpose of adapting treatment regimens. CTC-detection andcharacterization techniques hold promise for playing a role as a “liquid biopsy” that will allow physicians to follow cancer changes over time and to tailor treatment. Current research on CTCs is focusing on the identification of novel diagnostic and therapeutic biomarkers produced by these cells. CTCs are promising as novel tumor biomarkers because they are welldefined targets for understanding tumor biology and tumor cell dissemination that can open new avenues for the early detection of metastasis and its successful treatment. We discuss CTCs and their diagnostic potential with 4 leading scientists and clinicians in this field. A suggested reading list on this topic is provided in the Data Supplement that accompanies the online version of this Q&A at http://www. clinchem.org/content/vol57/issue11.