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CTC (Circulating Tumor Cell)



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CTC-mediated metastasis

What's CTC

Novel biomarker "CTC"

Recently, CTC tests that can quantify tumor cells in peripheral blood have attracted attention. "CTCs" stands for "Circulating Tumor Cells" and is defined as cells left from primary or metastatic tumor tissues and infiltrated into blood. It's thought that CTCs are present in minutely small quantity in the peripheral blood of solid cancer patients and some of them have metastatic potential to other sites.

 

History

90% of death in cancers is caused by metastasis from primary tumors to other organs. It is assumed that most of the cells which infiltrated from clumps of tumor cells into the blood vessel are destroyed by autoimmune system. However, very small number of them can slip through the attack of the autoimmune system, circulate in blood stream as CTCs and may establish metastases.

Study of CTCs has a long history. The existence of CTCs was first described in 1869 by Thomas Ashworth, a doctor in Austria, and twenty years later, the "seed and soil" theory was proposed by Stephan Paget, a surgeon in UK. The theory which suggests that a tumor cell - the seed - either sleeps or thrives within the unique environment of each organ - the soil was verified in 2003, and analysis of CTCs which is a "seed" in blood has been considered to be a very important field in clinical prediction. In 2004, a clinical study of CTC was reported showing importance of CTCs as a prognostic factor.

Reference: Paget, S. 1889. The distribution of secondary growths in cancer of the breast. The Lancet. 1:571-573

 

Clinical significance of CTC

Existing cancer tests

In cancer tests, prediction of the process regarding clinical condition of metastatic cancer is considered to be very difficult. Therefore, to obtain the correct information about the clinical condition of cancers is beneficial for its treatment.

Previously, process of clinical condition in cancers is diagnosed based on the examination and assessment of tumor size by imaging or quantitative assay of serum tumor markers as supporting information. Though imaging technique by CT scan is able to measure tumor size, it is not possible to know whether the tumor is proliferating or sleeping. And the imaging tests by CT scan are performed at a few month intervals to recognize the change of tumor size, so timely judgment of benefits of treatment is difficult. On the other hand, the level of tumor markers in serum correlates poorly with tumor size and can be elevated by inflammation independently of cancer disease condition. In addition, the serum tumor markers have concerns about correlation with treatment or change in cancer disease condition and furthermore an elevation of their level appears 4 to 8 weeks after anticancer drug treatment makes it more difficult to assess it.

It has been said to be important for effective cancer therapy that the doctors can obtain the information to know the correct disease status at any time during treatment. Therefore CTC test of peripheral blood has been coming to be recognized as a useful tool which can predict clinical condition of cancer disease.

 

Clinical significance of CTC

Clinical studies have reported that, cases of CTCs in peripheral blood of patients before initiating therapy and the cases with persistent CTCs even after treatment correlated with unfavorable prognoses. Additionally it has been reported that, in remarkable response cases of chemotherapy, number of CTCs decreased markedly after the first cycle of treatment.

Summary of expected clinical usability of CTC analysis

  • Determination of the need for aggressive treatment by the number of CTCs in blood before treatment.

  • Assessment of expected treatment effect by the number of CTCs in blood after the first treatment.

Clinical usability of CTC analysis is an earlier assessment of chemotherapy treatment effect by convenient method than the traditional diagnostic approaches. Monitoring of CTCs in blood can make it possible to determine the change drug or to have the option of terminal care. Meanwhile, combination of CTCs monitoring and imaging as CT scan is expected to provide more accurate information to know clinical state.

 

Characterization of CTC

Recently, in addition to enumerative analysis, there is also characterization research of CTC by examination of expressed biomarkers or variation/amplification/fusion of gene. In future, it may become possible to select an appropriate treatment for each patient by identification and understanding of CTC subgroups.


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