CTCs, Circulating Tumor Cells, are those cancer cells that have managed to get back into the blood stream. Thus CTCs are just what the name implies; malignant cells sloughed off and sent into the blood stream. Their point of origin may be unknown and they may actually be from a variety of locations if the cancer is metastatic and further the genetic makeup of each cell may be different depending on how the cancer may have progressed. What is certain is that they carry information as regards to the status of the malignancy and potentially its progression.
In a recent paper by Tseng et al the authors present an interesting summary of CTC and their identification. From Table 1 in the paper they characterize various ways to isolate CTS. We depict the results below:
As Tseng et al conclude:
CTC identification and characterization is meaningful for the interpretation of metastatic cancers (breast, prostate, colon, and lung cancer). The promise of CTC research in the early stages of cancer is largely unmet, requiring more sensitive and reproducible technologies. The “real-time biopsy” potential of CTCs is a key area for further intensive research and appropriate animal models provide the foundation for studies of the molecular regulation of CTCs in cancer and CTCs as biomarkers for therapeutic efficacy. The envisioned future is one in which a simple blood test will permit molecular tumor characterization, identification of treatment targets, and aid in the selection of the most appropriate targeted therapy from an armamentarium of agents.
The number of CTCs has a potential be an effective prognostic and predictive biomarker, which could assess therapeutic responses of metastatic disease in several cancers. The detection of CTCs in early stage cancer needs the further improvement of CTC assays. Since the heterogeneity of CTCs, the assays used to detect CTCs need tumor-specific rather than one technology for all cancer types. In conclusions, the better understand of the biology and clinical meaning of CTCs will help to improve CTC assays and further to apply in clinical utility.
In a PNAS article they indicate the complexity of CTC analysis:
Cancer patients have only between 5 and 50 CTCs per teaspoon of blood, so their presence is dwarfed by blood cells. However, in the past decade emerging technologies have, for the first time, allowed the isolation of CTCs from patients’ blood samples. Some methods, among the first established, rely on the cells’ physical properties. When a blood sample settles or is spun in a centrifuge, red blood cells, white blood cells, and other components of blood separate into layers. Based on their buoyancy, CTCs can be found in the white blood cell fraction. Then, because CTCs are generally larger than white blood cells, a size-based filter can divide the cell types.
Yet at the same time they seem to have prognostic value for many cancers. In the paper by Hu et al:
Perhaps more promising than enumeration is the ability to study CTCs in order to molecularly characterize a cancer. The ability to take a “liquid biopsy” at different time points in treatment creates opportunities for therapeutic decisions informed by the specific phenotype of a patient’s cancer, moving closer towards the goal of personalized cancer therapy. Molecular characterization of CTCs, however, represents new challenges. For example, whereas white blood cell contamination may be tolerable when detecting (“yes” or “no”) the presence of disease-related genetic aberrations (e.g., TMPRSS2-ERG fusion product), moving towards more quantitative analyses (e.g., mRNA transcript levels of gene expression) necessitates ultra-pure CTC samples. Technological improvements have helped overcome some of these obstacles, leading to early successes in genomic and transcriptomic profiling of CTCs, sometimes with as little as one cell….The role of CTCs in PCa is rapidly evolving. CTCs provide a window into the hematogenous spread of cancer and can drastically improve oncologic understanding and patient care. In metastatic PCa, CTC enumeration is an accurate method for monitoring disease and has been used in clinical trials as an intermediate endpoint. CTCs can be detected in localized disease and hold the potential to detect early metastasis. Perhaps the most exciting feature of CTCs is that they provide a platform for noninvasive, repeated inquiries into a cancer’s molecular behavior, ultimately enabling individualized, adaptive and more effective management of PCa over time.
Thus CTC have reached the stage of having potential for diagnostic and prognostic value. Their overall acceptance will take some time but they may have substantial merit.
 Tseng, J., et al, Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications, Cancers, V 6 pp 2369-2386, 2014. http://www.mdpi.com/2072-6694/6/4/2369
 Williams, S., Circulating Tumor Cells, PNAS | March 26, 2013 | vol. 110 | no. 13 | 4861
 Hu, B., et al, Circulating Tumor Cells in Prostate Cancer, Cancers 2013, 5, 1676-1690.