Friday, April 25, 2014

Circulating Tumor Cells


What is circulating tumor cells?
Circulating tumor cells are the lurking foes shed from primary tumor mess into a cancer patient's circulation systems, including blood and lymphatic systems.  circulating tumor cells (CTCs) are rare. How rare? In a metastatic cancer patient, typically it’s only 1 CTC per billions of red blood cells, or a single digit per 10 ml of blood. However, the rare CTCs act like dangerous seeds, lurking in the circulation and seeking new sites to lodge and grow. The tumor transfer to remote organs is called metastasis. 
Shocking Facts
 Metastatic carcinoma is the main cause of death in cancer patients. And the metastases are taking place via circulating tumor cells. In advanced colorectal cancer, patients with a CTC count >3 per 7.5ml blood had a worse therapeutic outcome [1]. In breast cancer, patients had CTC count of >5 per 7.5ml blood had significant shorter median survival (6.7 months) and overall survival (13.2 months). A study published in New England Journal of Medicine even revealed that the progression-free survival is only 2.7 months for patients who had CTC count >5 [2]. 
A Little More to Know
The only FDA approved CTC counting method is CellSearch (https://www.cellsearchctc.com/) CTC test. CellSearch system use magnetic beads coated with anti-EpCAM antibodies to target CTCS for enrichment and with immune-fluorescence labeling for identifying and counting. There is no approved method or drug to specifically kill CTCs inside human body.

The CELLSEARCH® System is the result of a commitment to innovation that began in 1999 and led to the first standardized, FDA-cleared, semi-automatic system that can capture and quantify circulating tumor cells from a 7.5-mL blood sample with a high level of sensitivity and specificity (adapted from CELLSEARCH website).
Current research work focuses on capturing, enumerating, and characterizing CTCs in blood samples [4]. The most commonly way to capture CTCs relies on the antibody that binds to surface protein. Through immune-labeling with either magnetic or fluorescence tags, CTCs can be isolated for imaging and analysis to recognize its molecular signature.
CTCs are seeding cells originated from primary tumor mass. Current research efforts on CTCs focus on methods of capturing, isolating, and identifying the cells for the purpose of diagnosis and characterization of phenotype signature. Lodging of the rare lurking foes results in the metastases of a tumor to remote organs and leads to fatal consequences. However, it’s still very hard to effectively find and capture the dangerous seeds. The figure shows a brief of recent research work [3].  
Another brief review of capturing cancer cells reported in The Scientist in April 2014 can be found at: http://www.the-scientist.com/?articles.view/articleNo/39503/title/Capturing-Cancer-Cells-on-the-Move/
Citations
[1] J Clin Oncol 26:3213-3221, 2008
[2] N Engl J Med 351; 8 781-791, 2004
[3] Science Vol.327, 26 Feb., 2010

[4] D. R. Parkinson et al., Considerations in the development of circulating tumor cell technology for clinical use. J Translational Medicin 10:138, 2012. 

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