A device that shines a laser on blood vessels (here, in a mouse) can detect scarce circulating tumor cells.
Ekaterina Galanzha/University of Arkansas for Medical Sciences
Tumors release cells into the blood that can reveal that the cancer is growing and spreading to other parts of the body. Now, researchers have shown they can train a laser device on the hand of a skin cancer patient and detect these scarce tumor cells coursing through the bloodstream. The device could one day improve screening for the cancer melanoma. It could also help doctors monitor whether treatments are working, and even curb the original tumor’s spread by zapping the roaming cells.
“It’s fascinating that it’s possible to detect these circulating tumor cells literally through the skin,” says medical oncologist Klaus Pantel of the University Medical Center Hamburg-Eppendorf in Germany, who was not involved in the study. But he and others caution that much work remains to show the device will help people with melanoma.
Most researchers who are working on ways to detect circulating cancer cells (CTCs) look for them in blood drawn from a person. In people with advanced breast, colon, or prostate cancer, doctors can order a commercial test that counts CTCs in such a blood sample. But these approaches often can’t pick up the few cells released by early cancers, and they don’t work for melanoma because its cells don’t sport the main surface marker that the tests use to detect CTCs.
Hoping to improve on other methods, a team led by biomedical engineer Vladimir Zharov of the University of Arkansas for Medical Sciences in Little Rock coupled a laser with an ultrasound detector to create what they dubbed the “Cytophone”—because the device detects cells acoustically. (“Cyto” means cell.) When they shine the Cytophone’s laser on an animal’s or person’s skin so that its light penetrates a few millimeters into near-surface blood vessels, any passing melanoma cells slightly heat up because of their dark pigment, melanin. This harmless heating creates a tiny acoustic wave that gets picked up by the ultrasound detector.
When Zharov’s team focused its device on a person’s hand for a few seconds to 1 hour and looked for signals against background noise from abundant, less energy-absorbing red blood cells, they detected no CTCs in 19 healthy volunteers. But in 27 of 28 melanoma patients, CTCs showed up as spikes.
The Cytophone can pick up a single CTC in 1 liter of blood, which is up to 1000 times more sensitive than other detection methods that probe for CTCs in a typical 7.5-milliliter blood sample, the team reports today in Science Translational Medicine. The device also detected small blood clots with the potential to grow and kill a cancer patient.
In an intriguing twist, when the researchers turned the laser to a higher but still safe energy level, they also showed that a patient’s CTC levels came down over the hour because the device was apparently destroying the cells, without causing any side effects. Although that’s unlikely to wipe out a person’s cancer altogether—the original tumor or metastatic tumors will keep releasing the cells—the Cytophone could be used to enhance the effects of a cancer drug, Zharov says.
The device could be used to follow whether an anticancer drug is working—if it is, a patient’s CTC levels should go down, says Zharov, who with his colleagues has patented the Cytophone and launched a company to develop it further. “You could monitor periodically every 3 months and see if the melanoma comes back.” It could also be used as an add-on to skin checks to improve screening for melanoma, like a mammogram for breast cancer, he suggests. And Zharov pictures using it to detect or monitor other cancer types by tagging patients’ CTCs with gold nanoparticles that, like melanin, would cause the cells to heat up.
But Pantel and others caution that those applications are a long way off. For one thing, the team only tested three patients with early stage melanoma. “They’re going to have to show they can find [CTCs] in early stage patients” by testing a much larger number, says oncologist Anthony Lucci of MD Anderson Cancer Center in Houston, Texas.
The researchers also need to explore whether the Cytophone can find CTCs in patients with darker skin—their higher levels of melanin in normal cells could make it hard for the Cytophone to distinguish any cancer cells, says mechanical engineer Shannon Stott of Massachusetts General Hospital in Boston. For now, she says, “It is a very cool study with lots of promise.”