Beyond counting: new way to use circulating tumor cells.

In 2007, researchers at Boston’s Massachusetts General Hospital (MGH) Cancer Center showed that a microfluidic device, the CTC-Chip, could separate and count rare circulating tumor cells (CTCs) in wholeblood samples (Nature 2007;450:1235–9). Last year, the team developed the CTCiChip, a refined version of its predecessor, and confirmed its utility in catching viable CTCs. This device can profile individual CTCs—including their DNA mutations and RNA and protein expression—at the molecular level (Sci. Transl. Med. 2013;5:179ra47; doi:10.1126/scitranslmed.3005616). Going further, the teams recently showed that CTCs captured with CTCiChip could be used to establish individual patient–based cell lines and xenograft models (Science 2014;345:216–20; doi:10.1126/ science.1253533). These cell lines can test for drug sensitivity, which researchers hope will facilitate individualized cancer treatment options. These findings took place in the MGH laboratories of Daniel Haber, M.D., Ph.D., Shyamala Maheswaran, Ph.D., and Mehmet Toner, Ph.D. The goal of culturing these cells ex vivo, according to Haber, is to enable functional analysis. Genetic testing for mutations often, but not always, is associated with drug response, he said. “Testing whether a drug really works in killing a cancer cell with a given mutation [would be] helpful. This becomes even more relevant when multiple mutations are present [in CTCs], each of which could be driving the cancer,” Haber said. CTCs are found in minute quantities in the blood of cancer patients, shed from either the primary or metastatic tumor. Research has statistically correlated CTCs with both patient survival and disease progression for certain cancers. Because a simple blood draw is appealing to both patient and clinician, researchers and companies have tried to detect and characterize CTCs in lieu of invasively taking a tumor sample. Still, most research on CTCs is confined to preclinical and academic studies. So far, the U.S. Food and Drug Administration has approved only one CTC detection tool: CellSearch. Made by Johnson & Johnson’s Janssen Diagnostics, CellSearch counts CTCs—those of an epithelial origin that express the surface epithelia cell adhesion molecule—in blood samples from breast, prostate, and colorectal cancer patients.