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Galletti et al. Using CTCs in prostate cancer

Investigation of other molecular makers in CTCs commercially available assays. Most of these
Intratumoral androgen synthesis has been identified as platforms are already commercially accessible
one of the mechanisms PC cells adopt to activate AR to the public as research tools to enrich CTCs for
signaling in presence of castrate levels of circulating downstream molecular analysis (i.e. RosetteSep™
androgens. Several steroidogenic enzymes are epithelial tumor cells enrichment kit, ISET filters).
®
involved in this process and the expression profiling Conversely, only CellSearch received FDA
®
of these molecules could be found altered in CRPC, clearance for CTC enumeration in solid tumors and
with overexpression of enzymes involved in androgen few other methods are performed in CLIA-certified
synthesis (SRD5A1, ARK1C3) and down regulation laboratories to interrogate specific key molecular
of enzymes implicated in androgen inactivation tumor markers (i.e. AdnaTest Prostate Detect and
(SRD5A2, CYP3A4, CYP3A5). Mitsiades et al. Epic Sciences™ for AR-V7) but the vast number of
[82]
evaluated the levels of expression of AKR1C3, technologies currently available for the enrichment
SRD5A1 and CYP17A1 by RT-PCR in CTCs isolated of CTCs enables researchers to examine nearly
from CRPC patients following EpCAM-based PBMCs any biological property of this cell population and
sorting. Even though no clinical correlations were potential implement that information into clinical
made between the expression levels of these enzyme practice.
and tumor response to ADT, the authors demonstrated
the feasibility of profiling key molecules in androgen The evaluation of tumor-specific alterations in
metabolism allowing the assessment and monitoring CTCs could potentially reveal clinically relevant
of potentially druggable targets. information to guide treatment selection based on
the molecular features of the disease in individual
EMT is a biological process that allows molecular patients. CTCs could be used to inform medical
changes and enhancement of the migratory oncologists about the major biological alterations
and invasive capabilities of the epithelial cancer of PC that have been shown to significantly affect
cells. [15] Many molecules and pathways have been treatment outcome. EpCAM-based approaches have
implicated in the regulation of the EMT-dependent been mostly adopted to perform these molecular
cellular plasticity and of its role in tumorigenesis [83] . analyses, however other emerging technologies
Recently, Ware et al. [84] identified a novel role of the
epithelial plasticity marker Snail in the induction of could also play a significant role in dissecting
enzalutamide resistance in PC. Even though a direct the biologic properties of PC CTCs, especially in
clinical evaluation of Snail in CTCs of PC patients diseases with more aggressive features.
has not been reported yet, Li et al. [85] proved the Clinical studies are currently ongoing to
feasibility of Snail expression levels assessment
by immunofluorescence in CTCs isolated from prospectively clarify the role of CTC-based
hepatocellular carcinoma patients. assessment of these molecular markers to predict
patient response and contribute to the era of
CONCLUSION precision medicine. However, the clinical utility of
a liquid biopsy-based evaluation of a predictive
CTCs first showed their clinical relevance more than marker still needs to be addressed with clinical
a decade ago, when it was reported that elevated trials in which any therapeutic strategy is planned
CTC counts were associated with tumor prognosis according to the liquid biopsy analysis.
and that changes in enumeration correlated with
treatment response in solid tumors. Nevertheless, The role of CTC enumeration has also been tested
CTC count is far from being used in the everyday in localized PC to identify those patients more likely
practice for lack of clinical utility. to relapse after radical treatment, and even in this
setting a clear correlation between CTC detection
CTCs rapidly demonstrated their full potential to and prognosis has been identified. However,
function as a true liquid biopsy and provide relevant whether or not adding CTC status in the panel of
biological information to describe the molecular the standard prognostic marker still remains an
portrait of disease. unanswered question.

It’s true that not all enrichment techniques are equal In conclusion, CTC analyses could provide crucial
and it is necessary to distinguish between platforms information on tumor biology, with the potential to
that are purely scientific tools and methods that enhance the quality and the efficacy of treatments
have to be regarded as clinically validated and with the ultimate goal of improving patient survival.
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ September 27, 2017 201