Cancer Blood Tests

Now Tewari and his colleagues at Fred Hutchinson Cancer Research Center in Seattle are excited about a discovery that may be the most promising way to detect cancer early: with a simple blood test. "Ultimately, the goal of all of this kind of research is to detect cancer early enough so that it can be cured," he says.

The team made the discovery partly by accident. They were studying short pieces of RNA called micro RNAs in human tissue samples. These tiny pieces of RNA, discovered only a few years ago, play a big role in regulating genes, and are now known to be altered in cancer.

Ordinarily, the researchers keep tissue samples cold because if they thaw, the RNA quickly degrades. But, recalls Tewari,"One of the samples had been left out at the bench for longer than it was supposed to. And the surprise here really was that the rest of the RNA molecules were all degraded, but the micro RNAs had completely survived.

"In addition to that, other labs had published some research also in the last few years, not looking at micro RNAs in blood but looking at micro RNAs in tissues that had been stored for long periods of time—and tissues in which the other kinds of RNA molecules get degraded—and they also had found, began to report, that these micro RNAs are quite stable in these tissues," he says.

That led Tewari to look for micro RNAs in blood samples. As they wrote in the Proceedings of the National Academy of Sciences, www.pnas.org micro RNAs are indeed surprisingly stable in blood.

"We then wanted to ask, even though we could find micro RNAs in healthy people, could there be micro RNAs in patients with cancer that were different than the ones that were there in healthy people?" he explains. They identified a set of micro RNAs present in prostate cancer tissues, but not in the blood of healthy people and figured out which might perform best in a blood test for cancer. Then they measured that micro RNAs in blood samples of 25 people with advanced prostate cancer, and 25 healthy people.

"In a large majority of the cases, just by measuring the amount of micro RNA in the blood, we could tell who had cancer and who didn't," Tewari says.

While there were some samples in which this particular set of micro RNAs was not enough to identify the cancer, Tewari points out that this experiment was a proof of principle.

He says the next step is to find the best micro RNAs for identifying each type of cancer and see how early they can be detected.

"We haven't developed a final blood test for detecting prostate cancer, especially not at an early stage," says Tewari. "But what we are very excited about is that it's proved the concept, it's proved the idea that not only are micro RNAs present in the blood and stable there, but micro RNAs arising from tumors can get into the bloodstream… and actually do get into the blood stream at levels high enough that we can detect them, and it—in our minds—opens up the possibility that this concept or this approach might be applied not to just prostate cancer but other types of cancer."

Amplifying Advantage

The technology for detecting micro RNAs very sensitively is already well-established, such as amplifying—making many copies—of small amounts of genetic material, commonly done in DNA fingerprinting in criminal cases.

Tewari says that's a big advantage over strategies that seek to use proteins as early signals of cancer. "Although that's an important line of investigation, it has some limitations, and one of the limitations is that proteins are quite difficult to identify and to detect. It's of course very possible to do that, but it's a lot of work to figure out a way to even detect one protein in a very accurate manner," he says.

The team's further studies will not only screen for more and better micro RNAs to signal cancer, but also study their functions.

"It's very possible that the kinds of micro RNAs that are circulating in the blood might reflect something about the tumor which might tell us which treatments might work better than others," Tewari says.

And "the blood tests that we would love to find are... ones in which we're not only detecting the cancer, but also finding those micro RNAs which are involved in actually causing the cancer because those RNAs—it might... be possible to manipulate them in some way or treat the cancer even in some way, by treating the micro RNAs," he adds.

In addition, the researchers want to know what is making micro RNAs so stable in blood and tissues, and whether that is related to their role in cancer.

Tewari now believes that there will be cancer blood tests in his lifetime. "I don't know when that's going to be, and there's a lot of work ahead and a lot of challenges," he says. "But absolutely, that's the goal, and that's why we do what we do."

This research was published in PNAS www.pnas.org Online Early Edition the week of July 28 - August 1, 2008, and was funded by: Pacific Ovarian Cancer Research Consortium, National Cancer Institute, Pacific Northwest Prostate Cancer SPORE, Core Center of Excellence in Hematology and the Paul Allen Foundation for Medical Research.