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A simple test for tumors

A new diagnostic for cancer could be as easy as a pregnancy test.

February 27, 2014

If you needed a diagnostic test for colon cancer and had a choice between a colonoscopy and giving a urine sample, which would you pick?

You’ve got plenty of company.

Stressful, time-consuming, expensive—those words describe many diagnostic tests for noncommunicable diseases (NCDs) like cancer and cardiovascular disease. But as the worldwide incidence of cancer and other NCDs increases over the next few decades, the need for such tests will grow.

Yet current state-of-the-art tests are beyond the reach of people living in resource-limited settings around the world. A central problem is the lack of reliable, easily detected biomarkers that signal the presence of a disease or condition.

Now a team of researchers, including David Wood of the Masonic Cancer Center, University of Minnesota, has reported success with a fresh approach to diagnostic testing. It consists of an injection, followed by a urine test for a biomarker that uses paper strips, like those found in a home pregnancy kit. The team, led by Sangeeta Bhatia of MIT, has published its work online this week in the Proceedings of the National Academy of Sciences.

“The problem with detecting NCDs is the lack of good biomarkers, so we made our own,” says Wood, an assistant professor of biomedical engineering at the University. “It can be detected without hi-tech instruments.” And instead of teams of doctors and nurses, the patient would be handled by just the person giving the shot.

Tricking tumors, uncovering clots

The researchers’ strategy used a bit of biochemical trickery. Here’s how they did it.

The backbone of the new technology is iron nanoparticles that, after being injected into a vein, carry specially designed molecules throughout the body. The researchers worked with mouse models of colon cancer and thrombosis. Thrombosis often occurs in air travelers when long periods of sitting lead to clots deep in veins; these can be very hard to detect.

The team took advantage of the fact that both tumors and clots contain elevated levels of certain enzymes. As a clot forms, the enzyme thrombin is elevated; it cleaves a protein that must be split in order to release the “building block” molecule of clots. And in tumors a certain type of “protease” enzyme is elevated. It cleaves a different protein, acting like a mini-machete to open a path for cancerous cells to escape into the bloodstream.

The researchers created probes by attaching a combination of two molecules to the iron nanoparticles. One was a synthetic analog of the protein the enzyme—either thrombin or the protease—normally acted on. Connected to it was a second synthetic ”reporter” molecule that would be set free by the enzyme’s action and end up in the urine, where it would signal the presence of a clot or a tumor.

In other words, the researchers presented tumors and clots with molecular messengers that tricked them into betraying their presence.

A reporter tells the tale

After injecting the probes into the mice, the researchers collected their urine and exposed it to strips of nitrocellulose paper coated with antibodies. As the urine flowed along a strip, it encountered lines containing antibodies that recognized tags associated with particular reporter molecules. If any line became visible, it meant the tumor or clot was present.

“This is a systematic injectable that goes everywhere in the body,” says Wood of the technology. “We know we can make a huge impact if we can start therapy early. If we can detect conditions easily, we can do triage and not waste money as we would, say, if we had to give everybody an MRI.

“This could be tailored to different cancers. One limitation is that most proteases [act on more than one protein]. But the beauty of this [system] is that you could use as many different markers and reporters as you want. Then, instead of worrying about getting the right marker lined up with the right cancer, you could use several, and the pattern of how much of each reporter comes out would indicate the cancer.”

Many of the materials in the system, including reporter molecules and iron nanoparticles, are already FDA approved, he says. MIT is working on a business plan to begin a startup to commercialize the technology and perform clinical trials.

Contact the writer at morri029@umn.edu

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