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Potdar CTCs in cancer diagnosis and treatment
Figure 2: Circulating tumor cells analysis in several epithelial cancers including breast, prostate, lung and colon cancer. CTCs: circulating
tumor cells
tumors and thus cannot be separated using the Cell proteins such as vimentin and fibronectin which are
Search Kit. Besides this kit, various CTC isolation responsible for invasive processes. [8]
methods are being established to isolate CTCs from
liquid biopsies, including the Ficoll Gradient Method, The CTCs are extensively studied in the diagnosis
the Islet Method, the Microfluidic Method and others. and treatment of breast cancer. Molecular profiling of
It is a very important task for cancer scientists to CTCs shows the progression of breast cancer and its
[9]
[10]
establish a precise method for isolation of CTCs response to therapy. Swaby et al. have described
from liquid biopsies, taking into consideration their HER2- breast cancer patients with HER2+ CTCs who
EMT phase and surface marker alterations during were given a trastuzumab-based therapy. This led
metastatic process. to a considerable revision in their treatment protocol
and proved that CTCs profiling is very important in
MOLECULAR PROFILING OF CTCS identification of the most useful therapy in HER2- breast
cancer patients. The CK19 and TP53 gene mutation
The CTCs can undergo a variety of changes during can also reveal the metastatic potential of triple-
the metastatic process and show heterogeneous negative breast cancer patients. In prostate cancer,
characteristics, causing difficulties in giving proper expression of the fusion of TMPRSS2 and ERG genes
treatment to cancer patients. Therefore, there is a and downregulation of PTEN have been shown to be
responsible for cancer causation. Schölch et al.
[11]
[12]
need to well characterize these isolated cells by gene have discovered a KRAS mutation in the CTCs of CRC
expression profiling. Molecular profiling of CTCs is patients whose primary tumor was KRAS wild-type,
therefore an integral part of CTCs analysis and provides suggesting that the sequence analysis of CTCs can
accurate phenotypes of these cancer cells. So far it better discover the presence of KRAS mutation.
[6]
is well established that certain genes are upregulated,
downregulated or mutated in several solid tumor Treatment of other cancers can also benefit from CTCs
malignancies and their analysis can help in proposing analysis. This analysis is especially useful in lung
targeted therapies to treat many of these cancers. cancer because repeated biopsies are not possible
A major phenomenon seen in CTCs in metastatic in these patients. Evaluating mutations on exon 19
cancer is their transformation during EMT transition. and 21 of the EGFR gene are the prime determinant
During the EMT process, CTC cells go through for drug-based therapies in lung cancer. In addition,
several modifications at both cellular and molecular mutations such as T790M, EML4-ALK rearrangement,
levels. There is downregulation of E-cadherin genes BRAF, KRAS, HER2, PIK3CA/AKT1, ROS, FGFR1,
[7]
and upregulation of TWIST1 and TWIST1 genes. In and MET can all be studied for lung cancer
addition, there is an upregulation of extracellular matrix treatment. Overexpression of H-RAS oncogene and
[13]
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ January 12, 2017 3