The Researchers from the University of Wisconsin-Madison, in the journal Clinical Cancer Research, demonstrated improved methods of capturing free-floating cancer cells that are cast-off from tumors and circulating in the blood. If these cast-off cells can be accurately counted, they could provide an additional way to track treatment or screen for the disease.
Tumor cells circulating throughout the body in blood vessels have long been feared as harbingers of metastasizing cancer – even though most free-floating cancer cells will not go on to establish a new tumor. But if these cast-offs could be accurately counted, they could provide an additional way to track treatment or screen for the disease.
The new researchers demonstrated that by forcing cancer cells to slow down and developing stronger molecular traps specific to circulating tumor cells (CTCs), they could identify large numbers of the cells in cancer patients undergoing radiation therapy.
The number of CTCs dropped during therapy and subsequently rebounded in those patients that ended up requiring additional treatment – suggesting that this technology could supplement other techniques for tracking the progress of treatment.
University of Wisconsin-Madison Professor of Pharmacy Seungpyo Hong and his collaborator Andrew Wang of the University of North Carolina School of Medicine started the company Capio Biosciences in 2015 to commercialize the technology, which they term CapioCyte.
Scientists have recognized CTCs as potentially useful metrics for tracking a patient's disease for some time. But the cells are the proverbial needle-in-a-haystack, drowned out by billions of ordinary red blood cells and other cells found in the blood.
The CTCs attach themselves to blood vessel walls and begin tumbling along looking for suitable places to invade. This behavior separates them from the oxygen-carrying cells floating by and is mimicked in the CapioCyte technology using an array of sticky proteins that force the CTCs to begin rolling, which slows them down.
The cells are then trapped using a series of three cancer-specific antibodies, proteins that tightly bind and hold onto the CTCs. Then the researchers developed a nanoscale structure shaped a little like a tree, with each branch tipped with an antibody. As a cancer cell passes nearby, many individual branches can latch on, increasing the strength of the attachment.
The cell rolling and multi-tipped branches helped the researchers capture an average of 200 CTCs from each milliliter of a patient's blood, many times the number of cells captured with previous technology. They identified cancer cells in each of 24 patients undergoing treatment for head-and-neck, prostate, rectal or cervical cancer that enrolled in the study.
"The absolute numbers of CTCs don't represent too much because there's too much variation individually, but the more important thing we found was the trend – how the CTC numbers change over time upon treatment. So, for example, we've shown that the CTCs go down when the patients are responding really well to the radiotherapy," says Hong.
Although the number of cells did not correlate with the stage, and thus severity, of the cancer, the reduction in cells was correlated with successful radiation therapy. In two of the three patients that had the recurring or persistent disease, CTC numbers came back up.
"Our data suggest that we have a good chance of making CTCs a predictive biomarker or biomarker for surveillance for at least a few cancers, and that's always exciting," says Wang.
"What makes us excited in particular is we can see the direct impact," says Hong. "As a researcher, if you develop a new technology and it can directly help people, that's going to be the most rewarding experience – it's really exciting."