What are circulating tumor cells? These cells, known as CTCs, are ghosts, echoes of a distant metastatic tumor that enter the bloodstream every once in a while. They’re not necessarily the seeds of a brand new tumor, riding the bloodstream like commuters until they find the right stop for their next franchise. Instead, most CTCs just seem to drift like fallen leaves in a creek, swirling aimlessly in the blood. Eventually, most of them die and are washed away; rarely, a few may go on to establish new metastatic tumors.
Scientists have known about CTCs for more than a century, regarding them as elusive prizes for study. “These cells provide a means for us to study a cancer noninvasively, without the need for surgery or a biopsy,” says scientist Shawn Lupold, Ph.D., The Nancy and Jim O’Neal Scholar. “The real challenge has been to capture, analyze, and quantify these rare CTCs among the enormous background of blood cells, lymphocytes, dead cells, and debris.” But how to find and seize these cellular four-leaf clovers? Lupold and colleague Ron Rodriguez, M.D., Ph.D., The Irene and Bernard L. Schwartz Scholar, along with research associate Ping Wu, believe the common cold virus may be able to help.
The scientists have plenty of experience using specially engineered viruses as cancerseeking missiles, tailoring them to target and kill only prostate cancer cells, or even more specifically, cells that make a particular product, such as prostate-specific membrane antigen (PSMA). Although there are promising assays on the market that can capture CTCs in the blood of people with metastatic breast, colon, or prostate cancer, and use the number of CTCs found to help predict the course of disease, “these assays are still struggling to achieve high sensitivity and purity,” says Lupold, “and to provide additional valuable information such as CTC viability, tumor gene expression patterns, and genetic mutations.”
Building on their past work with recombinant viruses, the Brady investigators are looking to build diagnostic agents capable of deciphering whatever information can be gleaned from CTCs. They don’t want to kill these cells; they want to learn from them: Imagine using a heat-seeking missile and blowing up the Loch Ness monster instead of spotlighting it, watching it, and solving its mysteries.
They don’t want to kill these cells;
they want to learn from them.
Imagine using a heatseeking
missile and blowing up the
Loch Ness monster, instead of spotlighting it,
watching it, and solving its mysteries. Oops!.
Oops! “What we’re doing,” explains Lupold, The Nancy and Jim O’Neal Scholar, “is engineering this virus to cause infected cancer cells to secrete a highly detectable, luminescent molecule from a tiny crustacean called Metridia longa. This is all accomplished in a blood sample, not the patients themselves, to give us information about CTC levels.” The recombinant virus only “lights up,” or “reports,” if it detects prostate cancer CTCs. The level or intensity of this signal may indicate a larger amount of cancer, or a more aggressive cancer.
“The rationale for this approach is multifold,” Lupold adds. “The adenovirus reporters only detect living cells, and the ones they detect should be cancer-specific.” One problem with current CTC assays is that they seem to get distracted by background noise – leukocytes, cell debris and other flotsam in the crowded bloodstream. This new diagnostic study is funded by an idea development award from the Department of Defense. “Our team of researchers is now optimizing this assay to determine its sensitivity and specificity. We are also evaluating whether this new approach can detect CTCs in a small series of patients with localized and metastatic prostate cancers,” says Rodriguez.