Peter Kuhn, PhD, a professor of cell biology at Scripps Research Institute in La Jolla, Calif., has called circulating tumor cells "the messenger and the message of metastasis."
 
"If we can understand CTCs, we can understand metastasis," he said.
 
Dr. Kuhn, a biophysicist by training, has taken a different approach to characterizing CTCs. His team's "fluid biopsy" involves spreading a layer of all nucleated cells found in the blood on a glass surface, adding fluorescent antibodies to cytokeratin, an essential component of CTCs, and scanning the slide for sites of fluorescence. After some high-performance computation that weighs the cellular parameters, cellular pathologists then do an in-depth analysis of each marked cell to see if a CTC lurks there.
 
Dr. Kuhn's group has licensed the technology to California's Epic Sciences and is collaborating with Microsoft's high-performance computing team to manage the vast trove of data a fluid biopsy generates. They are now being validated in observational studies at nearly a dozen clinical sites around the country and although Dr. Kuhn said he would like to see it FDA-ready by 2014, he recognizes the hurdles involved.
 
Freely admitting a bias for his team's approach, Dr. Kuhn suggested that the CellSearch assay is limited in its utility. According to Quest Diagnostics, a medical testing service, antibodies used in the CellSearch assay are targeted at EpCAM and cytokeratins 8, 18 and 19, cell markers expressed by adenocarcinomas. CTCs that do not express these markers will not be detected by the assay, while circulating epithelial tumor cells from malignancies other than metastatic breast, colorectal or prostate cancer may be detected.
 
"What we need is a test with true predictive value, a true drug stratification test," he said. "And we need to develop this test for each and every drug. Nobody is quite there yet, but we are all working on that goal."
 
The Tipping Point?
 
Unlike others in the field, Dr. Kuhn believes that CTCs can be identified in the bloodstreams of patients with virtually any type of cancer, once the right technology is developed and the right assays are applied. "We have a 'no cell left behind' approach-we're not enriching for a particular cell," he said. "Most people are enriching for particular cells, so that becomes a selection process, and you will only find that particular subtype."
 
For Dr. Kuhn-and many others-the real value of the fluid biopsy goes beyond predicting prognosis or even effectively changing treatment strategies midstream.
 
"The ultimate utility for the biomarkers we identify in these cells is the predictive power for a specific drug molecule," he said. "After ASCO 2011, with the success of Pfizer�s crizotinib and Plexxikon's vemurafenib, I would argue that we are now looking back at the tipping point of personalized cancer care. It is here to stay, and overlaying it with the fluid biopsy will be one way that we can accurately identify patients for these new agents. Will there be one test that will do it all? No. We need to understand how the fluid biopsy provides us insight into each subtype of disease. That�s not going to fall out of the sky. We need serious clinical studies that ask very specific clinical utility questions with validated approaches."
 
-Gina Shaw