Page 56 - Read Online

basis of HER2 expression has been suggested in many an optimal treatment for a given patient. It has been
[62]
cases. CTCs vary in expression and frequency of this reported that the presence of genes like EpCAM, CCNE2,
gene, and it can be directly correlated with the disease’s DKFZp762E1312, EMP2, MAL2, PPIC, or SLC6A8
progression and survival. Not only about correlating can be related with the presence of CTCs in peripheral
[54]
the primary tumor’s characteristics, CTCs can reveal blood. [56,62]
more vital information, which is at times not detected In breast cancer, chemotherapy is one of the standard
by mere analysis of primary tumor. In a particular group modes of treatment. During the course of this therapy,
of HER2- breast cancer patients, HER2+ CTCs are CTCs values are determined before and after rounds of
identifi ed. This leads to consideration of revision in chemotherapy. In most of the cases with non-metastatic
[55]
the ongoing treatment of the disease. Trastuzumab-based state of breast cancer, reduction in number of CTCs is
therapy is applied to these patients with HER2+ CTCs observed after the fi rst round of chemotherapy. However,
and HER2- primary tumor. This study has shown that 1 it was also noted that CTCs had a tendency to attain
out of 4 patients are treated completely while 2 patients resistance to the therapy. Hence, it is suggested that
have attained partial response to this treatment. Even a regimen of increasing doses should be deployed in
though this study number of patients are few, it has given [63]
important facts about CTCs. It has helped in identifying the progressing rounds of chemotherapy. Studies by
[64]
the changing course of the disease well before time. Peeters et al. have revealed some statistics about
Thus, CTCs hold the potential to represent the metastatic CTCs count and disease state. In a small group under
state of HER2- breast cancer. [55] their study, about 80% of patients who had more than
80 CTCs in 7.5 mL of blood died within one year
CTCs have been reported to harbor many types of from diagnosis of metastasis of disease. In a similar
mutations and transformations. Obermayr et al. have study by Smerage et al., it has been observed that
[56]
[65]
shown that genes like EpCAM and secretoglobin, family CTCs continued to remain detected after fi rst round of
2A and SCGB2A2, can be used as important markers chemotherapy in some patients of breast cancer. It is
in the detection of CTCs in breast cancer. CTCs have observed that such patients are in rapid progression of the
been reported to establish mutations after dissemination disease to metastasis. They have further suggested that
from the primary tumor and some of these mutations in such cases, it can be ideal to opt for some alternative
may help the circulating cells to attain enhanced survival treatment with some of the novel therapeutic agents
and therefore molecular profi ling of CTCs holds the rather than continuing with the same chemotherapy. [66]
importance in understanding the real state of disease.
Monitoring the CTCs with respect to CK19 expression CTCs in Prostate Cancer Diagnosis and
can reveal the nature of metastatic potential of the Treatment
tumor. CK19 expression in CTCs has been prognostic Prostate cancer originates in the prostate gland of male
for worse overall outcome of the disease. CK19 as well reproductive system. Fusion of TMPRSS2 and ERG
as TP53 mutations are mostly found in all of the CTCs genes is identifi ed as one of prime reasons leading to
derived from triple negative breast cancer patients. prostate cancer which is often accompanied by loss of
[57]
Some researchers believe that it can be one of the driving PTEN. Biopsy remains the test for full confi rmation
[67]
factors to the progression of the disease to triple negative of this disease. Less invasive processes are sometimes
[53]
stage. It has also been shown that breast cancer patients conducted to detect this disease as well as to understand
which expressed KRT19, SCGB2A2, and ERBB2 genes its progression. Prostate-specifi c antigen (PSA) level
[56]
showed poor survival rates. IGF-IR mutation has also detection is one of such tests which can be used to
been observed to be expressed in patients of breast cancer identify the presence of disease and monitor the treatment
at a metastatic stage of disease. Furthermore, mutations in effect in these patients. However, PSA levels may not be
PIK3CA gene and ERBB2 mutations are reported in CTCs always necessarily indicative of the disease progression
of some patients whose primary tumor did not share this as PSA level may raise due to reasons other than prostate
state of disease. [57,58] Apart from these mutations, EMT cancer. Similarly, fall in levels of PSA during treatment
changes have been one of the critical properties of CTCs. may not be necessarily indicative for the eradication of
Most of the CTCs isolated from breast cancer patients the prostate tumor. It has been shown that drugs targeting
show the presence of EMT markers such as ETV5, androgen receptor (AR) may bring down levels of PSA
[41]
NOTCH1, SNAIL, TGFB1, ZEB1, and ZEB2. The but not necessarily cure the disease simultaneously.
mutational and transitional changes taking place in CTCs Hence, a better prognostic marker is greatly demanded.
make them gain an aggressive behavior which in turn When PSA testing falls insuffi cient to validate the
helps them to break apart from the basement membrane course of treatment, CTCs isolation enumeration and
and disseminate from the tumor. EMT pathway and characterization can act as a reliable marker for diagnosis
[59]
PIK3CA mutations have been related to progression of the and therapy of prostate cancer. [68,69]
disease to metastasis in many cases. [60,61] Hence, molecular
[70]
profi ling of CTCs is becoming increasingly important In a study by Attard et al. have captured circulating,
both to understand the state of the disease and then select non-apoptotic nucleated, EpCAM+ CK+ CD45- cells
Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦ 49