Circulating tumor cells (CTCs) are, by definition, epithelial cells with an intact nucleus that express cytokeratin and don’t express the leukocyte-common antigen CD45, which are found in the blood of cancer patients.
Their presence and abundance in patients who have undergone treatment has been shown to correlate with disease progression and overall survival. They are extremely rare even in such patients: estimates are in the range of 10-8–10-9, and 50 from a milliliter of blood is considered a good yield.
Yet no one truly knows what CTCs are, where they come from, what they mean, what the best way is to get at them, or even what to with them afterward. There is a single FDA-sanctioned technology, Veridex’ CellSearch, approved only for the semi-automated enumeration of CTCs from 7.5 mL of whole blood.
That doesn’t stop other techniques—some of which build upon the CellSearch platform, others utilizing distinct technologies—from generating a lot of excitement as well. Academic scientists, physician-researchers, and industry players gathered at Select Biosciences’ inaugural “Circulating Tumor Cells” conference to discuss how to capture, analyze, and interpret the data from these putative biomarkers that many feel have the potential to significantly impact clinical oncology.
Minetta Liu, M.D., associate professor at Georgetown University Medical Center, uses CellSearch for “all of my patients within the indication of metastatic disease, and I have found it useful in timing imaging studies, in helping to determine in conjunction with routine clinical factors and our radiological studies whether current therapy is helping a patient or not,” she said. “We don’t know what we’re counting, but I do know that counting the cells with that technology does correlate with patient outcomes.”
The hope is to go beyond simply enumerating CTCs. “We need to figure out what these cells are so we can manipulate them, to do better in those outcomes,” she added. Dr. Liu is involved in a clinical trial comparing molecular features of CTCs with those from primary breast tumor or metastatic sites, “trying to get an understanding of what these cells are trying to tell us.”
Stefanie Jeffrey, M.D., chief of surgical oncology research at Stanford University School of Medicine, is interested in how CTCs may be used to individualize therapy. Even from the same blood draw you can see different types of CTCs, and this may have implications for treatment, especially in a metastatic setting. One drug may be needed to treat one kind of metastasis and another drug to treat another, but you usually cannot biopsy all metastases a patient has.
“If you could do a liquid biopsy in real time, and could see how the tumor cells are changing, then potentially you may be able to more intelligently select the therapy—but this would have to be proven within a prospective clinical trial,” Dr. Jeffrey said. “We’re hoping that CTCs that are released to the bloodstream may be a surrogate, representing some of the cells that are involved in the seeding and reseeding of metastases.”
Lihua Wang, M.D., Ph.D., senior scientist of laboratory of toxicology and pharmacology at Frederick National Lab, develops CTC assays for targets that have been demonstrated for tumors, to have a way to measure the effect on tumor cells multiple times after administration of a drug—the assumption being that what’s happening in the CTCs is accurately reporting what’s happening in the tumor. But this needs to be proven. In fact, one of Dr. Wang’s fundamental goals is to establish whether a CTC is an equivalent to a biopsy.
A true surrogate not only accurately reports the same effect on its target, but reports it quantitatively as well. For the assays they have looked at there is concordance, she noted. “We have not yet proven that it’s a surrogate. That’s a high hurdle.”