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Advancements Being Made in Methods to Detect Circulating Tumor Cells for Cancer Treatment

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February 25, 2011
Scientists are working on ways to detect cancer cells that may circulate in the blood long after the removal of the primary tumor. Current studies show that the identification and monitoring of circulating tumor cells (CTCs) may be useful in predicting possible metastasis, disease progression, and/or response to treatment.

What is metastasis?

Normal cell growth is a complex process and has been studied in depth for many decades. Abnormal cell growth, as seen in various cancers, is an even more complex process with millions of dollars spent each year pursuing a better understanding of how and why cancer cells grow and spread.

One of the major concerns in cancer patient management is the prompt detection of possible spread (metastasis) of cancer cells to other tissues. Tumors grow because they have access to nutrients delivered through blood. As they grow, cells may slough off and be transported through the blood and/or the lymphatic system. Metastasis occurs when these circulating tumor cells (CTCs) implant themselves in other tissues.

Once diagnosed with cancer, patients are followed using a variety of procedures to detect metastasis and best determine the status of their disease. Performing a blood test to detect CTCs is a less invasive procedure than the more traditional means of determining the extent to which a cancer may have spread, such as tissue biopsies and bone marrow aspirations. Measurement of CTCs may be more sensitive, quicker, and less expensive and time-consuming than other procedures like mammography and bone scans.

While the largest studies on CTCs have been done with breast cancer patients, researchers are looking at melanomas and other tumors such as prostate, colorectal, and lung cancers. These studies have shown that identification of increased number of CTCs in blood may play an important role in predicting metastatic cancer. There is also some evidence that this type of testing may help in establishing the prognosis for a newly diagnosed patient.

Detection of CTCs

The presence of CTCs in blood is very low, as few as 1 CTC per 100,000 to 10 million nucleated cells. A variety of techniques have been developed over the years to detect and isolate CTCs. They include physical separation of cells using a complex filtration system, various immunologic techniques using monoclonal antibodies; a combination of immunologic techniques and microarray technology, and various molecular procedures such as reverse transcriptase polymerase chain reaction (RT-PCR). Each of these techniques offers unique opportunities to identify CTCs but also have certain technical limitations. One of the limitations is in the number of cells that can be detected. Currently, investigators are looking for the most optimal process that ensures accuracy, timely testing, and cost-effectiveness.

Second generation technology

While various techniques have been used to isolate CTCs, one very promising prospect is an assay being developed through a partnership between Boston's Massachusetts General Hospital (MGH) and Veridex, a subsidiary of Johnson & Johnson (J&J). Recently, they announced that they will work together to develop a new, second-generation technique that both detects the spread of cancer and analyzes the presence of tumor cells in response to treatment.

Second generation technology using combined immunotechniques and automation is now being tested at MGH, Memorial Sloan-Kettering Cancer Center in New York City, MD Anderson Cancer Center in Houston, and Dana-Farber Cancer Institute in Boston. Funding for this study and development of the second-generation technology came from the September 2008 Stand Up to Cancer Telethon. This advanced technology will allow for counting, capturing, and characterizing tumor cells found in a patient's blood.

Current research in developing CTC technologies is encouraging but interpretation faces many challenges, according to a recent paper published in the British Medical Bulletin. The authors discuss the various technologies, including that developed by MGH and Veridex. The potential in analyzing for the presence of CTCs is quite encouraging in how it applies to personalized cancer therapy. For example, if a person has cancer and the treatment is not reducing the number of CTCs, it may be beneficial to change therapy. Yet, there still is a need for further study aimed at improving specificity, sensitivity, and reproducibility of CTC assays. The ability to separate tumor cells from normal, non-cancerous cells is an ongoing process. The need for additional testing on a larger scale to validate CTC test accuracy and efficacy is still required.

Furthermore, the significance of CTCs in cancer management is still being studied. Questions remain about whether the presence of CTCs truly indicates cancer's spread or recurrence. There is concern that tests that detect small numbers of CTCs may lead to overdiagnosis and unnecessary treatment. Additional research is required to determine if a person with detectable CTCs would indeed have a worse prognosis and require more cancer therapy or whether a few CTCs in the blood may be harmless.

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Press release. MGH Cancer Center receives $15 million grant from SU2C. Massachusetts General Hospital. Available online at http://www.massgeneral.org/cancer/about/newsarticle.aspx?id=1719 through http://www.massgeneral.org. Issued May 29, 2009. Accessed January 20, 2011.

Brenda Goodman. New Push to Develop Cancer Blood Test Researchers Announce Plans to Develop Test That Detects Circulating Tumor Cells. WedMD. Available online at http://www.webmd.com/cancer/news/20110103/new-push-to-develop-cancer-blood-test through http://www.webmd.com. Published January 3, 2011. Accessed January 20, 2011.

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Press release. Veridex, LLC Announces Collaboration to Develop Next-Generation Circulating Tumor Cell (CTC) Technology with Massachusetts General Hospital. Available at http://www.jnj.com/connect/news/all/Veridex-LLC-Announces-Collaboration-to-Develop-Next-Generation-Circulating-Tumor-Cell-Technology-with-Massachusetts-General-Hospital through http://www.jnj.com and at http://www.prnewswire.com/news-releases/veridex-llc-announces-collaboration-to-develop-next-generation-circulating-tumor-cell-ctc-technology-with-massachusetts-general-hospital-112796484.html through http://www.prnewswire.com. Issued January 3, 2011. Accessed January 20, 2011.

UPDATE: Veridex, Mass General to Develop Platform for Circulating Tumor Cells. Genome Web. Available online at http://www.genomeweb.com/dxpgx/update-veridex-mass-general-develop-platform-circulating-tumor-cells through http://www.genomeweb.com. Published January 3, 2011. Accessed January 20, 2011.

Interview with Johnson and Johnson spokeswoman Devon Prutzman. January 20, 2011. Conducted by Deborah Levenson for Lab Tests Online.

Interview with Massachusetts General Hospital technology co-developer Mehmet Toner. January 24, 2011. Conducted by Deborah Levenson for Lab Tests Online.

Gerges N, Rak J, Jabado N: New technologies for the detection if circulating tumour cells. Br Med Bull 4:49-64, 2010. Available online at http://bmb.oxfordjournals.org/content/94/1/49.full.pdf+html through http://bmb.oxfordjournals.org.

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H. Gilbert Welch, special to CNN. Cancer Breakthrough, or nightmare? January 11, 2011. Available online at http://www.cnn.com/2011/OPINION/01/11/welch.overdiagnosed.cancer/index.html?npt=NP1 through http://www.cnn.com. Accessed February 17, 2011.

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