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[1].
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[2]:
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[3]:
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.
[1]
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
[2]
Williams, S., Circulating Tumor Cells, PNAS | March 26, 2013 | vol. 110 | no.
13 | 4861
[3] Hu,
B., et al, Circulating Tumor Cells in Prostate Cancer, Cancers 2013, 5,
1676-1690.
Posts
