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from prostate cancer patient’s blood and confi rmed this method. Galletti et al. made use of prostate
[81]
for their malignant origin and hormone-regulated cancer-specifi c antibodies i.e. prostate-specifi c membrane
expression of ERG1. Thus, CTCs hold great potential antigen, PSA, prostate specifi c stem cell antigen and
to identify and stage the prostate cancer with minimal EpCAM to evaluate isolation of CTCs in the metastatic
invasive procedures. Giesing et al. have identifi ed stage of disease which might escape EpCAM specifi c
[70]
[71]
overexpression of fi ve genes, namely, SOD2, GPX1, selection. They have indicated isolation of specifi c
AR, cyclin B, and bFGF which have predicted the CTCs including the one which undergoes EMT and
clinical stage of metastasis and 3 of these genes are escape EpCAM selection and organ-specifi c CTCs in the
related to bone metastasis. CTCs are known for their metastatic stage of prostate cancer. [81]
[72]
heterogeneity acquired due to frequent transitions from
epithelial to mesenchymal state. Some of these EMT CTCs in Colorectal Cancer Diagnosis and
mutations are more frequent in castration-resistant Treatment
prostate cancer than compared to hormone-sensitive Colorectal cancer (CRC) is one of the most dreaded
prostate cancer. They can be used to identify specifi c diseases and has its poor prognosis. Although survival
targets in variants of the same type of cancer. These rates have drastically improved over time, timely
mutations can be used as a checkpoint and also help to prognosis would aid the treatment to a great extent using
speed up this testing as well as validation of upcoming CTCs testing. The data available for earlier stages are
therapies. In prostate cancer, CTCs have been proposed yet bare and lacks good sample size for studies on CRC.
to act as intermediate or surrogate endpoints for survival Romiti et al. have analyzed the prognostic role of
[82]
and to shorten timelines for drug approval. [73,74]
CTCs, highlighting the importance of CTCs count before
Changes in levels of CTCs can be correlated with the and after chemotherapy. However, to avoid misleading
disease status. Patients with lower levels of CTCs have CTCs counts after surgery, it has been suggested that
shown slower disease progression in comparison to those there should be a time gap of at least 24 h prior to
having a higher amount of CTCs. CTCs are sure to post-surgical sampling. This is because the procedure
[75]
provide a better overall picture of the state of disease may contribute to a temporary rise in CTCs which are
as there are molecular variations in different sites of rapidly cleared within 24 h. CTCs follow-up for patients
metastasis. Shaffer et al. demonstrate an example of with the aggressive disease can form an inevitable tool
[76]
variation in EGFR ranging from 0% to 100%. Hence, and also help in selecting better emphatic treatments. [82,83]
[84]
understanding the heterogeneity in the disease cannot be Barbazán et al. have done molecular profi ling of CTCs
understood from the single site biopsy and profi ling of derived from metastatic CRC. They have studied various
[77]
these CTCs becomes a necessity. Leversha et al. have molecular markers, such as VCL, ITGB5, BMP6 for
shown that molecular characterization of CTCs may be invasive phenotype, TLN1, APP, CD9, LIMS1, and RSU1
possible for reporting genomic amplifi cation of AR and for adhesion and migration for deeper understanding
chromosomal instability in prostate cancer patients. There of the behavior of these prostate cancer cells. These
is very much high expression of MYC and TMPRSS-ETV markers can be used to profi le the type of tumor and to
[77]
genes and downregulation of PTEN. Such copy assist in selecting a suitable treatment. In some reports,
number alterations have been related to aggressive researchers claim that a higher amount of CTCs is
[78]
tumors. CTCs exome sequencing has proven its clinical reported in mesenteric blood rather than peripheral blood.
signifi cance. Major percentage of cancer mutations are CTCs can be used to diagnose patients symptomatic for
detected in CTCs, which matched the primary tumor. CRC in addition to fecal occult and lower gastrointestinal
[85]
Furthermore, a great percentage of mutations could be endoscopy. Like other malignancies, dormancy of
predicted and matched with the metastatic site of tumor. CTCs in CRC is another aspect to discuss because even
The presence of more than 5 CTCs in 7.5 mL of blood after signifi cant exposure to treatment, some CTCs
has been related to poor outcome of the disease treatment continue to be detected in the circulation. Molnar et al.
[86]
[75]
in metastasis. Hence, not only is it benefi cial in mention about detection of CTCs as individual cells or as
providing prognostic information, but it can also act as a clusters by a CK-based, immunomagnetic cell separation
gateway to treat those patients in a better manner whose method. Although the number of CTCs decreases with
tumors do not shed CTCs. [79] the progressing treatment methods, at least a few of
these cells or clusters are observed to be circulating in
Newer technologies continue to emerge with the growing the blood stream for a long time despite operation. This
research. Lu et al. have introduced NanoVelcro CTCs could be explained by assuming that some CTCs remain
[34]
chip which claims to have better and reproducible dormant in condition for long durations and that they still
results as compared to FDA approved CellSearch kit. continue to be present in the circulation.
®
Olmos et al. have made use of reverse transcription
[80]
polymerase chain reaction (PCR) to identify telomerase Mutational analyses of CRC derived CTCs carried out by
activity in CTCs for which they are very sensitive. Bork et al. have pointed out some clinically signifi cant
[87]
However, individual CTCs can be identifi ed with characteristics. In particular, KRAS mutant CTCs are
50 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦