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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
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