Scientists in Chicago and around the country are racing to develop pinprick blood tests that can reveal some of the most deadly and hard-to-detect cancers in their early “silent” stages, when they are most curable and most elusive.
Researchers are working first on ovarian cancer, a disease that is a death sentence for about 90 percent of the 20,000 American women diagnosed each year. Because ovaries are hidden deep inside a woman’s body, finding the cancer is difficult and usually comes too late for curative therapy.
A blood test, still in research, holds the promise of making the diagnosis as easy as drawing a drop of blood, placing it into machinery that spits out a bar code, then having another computer scan the bars for a pattern distinct to ovarian cancer.
The test is potentially the first big benefit to come out of the new science of proteomics–the study of thousands of proteins at the same time. Different types of cancers produce distinct proteins, depositing them in microscopic amounts in the bloodstream. Proteomics is allowing scientists to map the thousands of proteins in blood and hunt for the telltale signs of cancer lurking somewhere in the body.
Researchers are using the emerging technology to look for protein signatures for cancers of the prostate, breast and lung, with early promising results.
In most cases, scientists don’t even know why the cancer produces the proteins they are looking for–but they don’t need to know that to see patterns that reveal hidden diseases.
“We’re going from detecting the needle in the haystack to detecting multiple needles in the stack,” said Dr. David A. Fishman, a Northwestern University gynecologic oncologist.
The technology also is being evaluated for its ability to diagnose infections and to quickly spot side effects from drug treatments and exposure to anthrax or other bioterrorist weapons.
Fishman directs a sprawling laboratory at Northwestern’s medical school, where he oversees the National Cancer Institute’s National Ovarian Cancer Early Detection Program. With 26 other centers around the U.S. and other countries collaborating in the program, it is the largest in the world.
The group helped score a breakthrough with the blood test, developed by Dr. Lance Liotta of the institute and Emanuel Petricoin of the U.S. Food and Drug Administration, in conjunction with Correlogic Systems Inc., a Bethesda, Md., company.
The test takes a drop of blood from a finger stick and hits it with a laser. Energy from the laser activates tens of thousands of proteins found in blood so that a mass spectrometer can sort them out by charge and size. That is converted into a long code, which looks chaotic and meaningless to the human eye.
Using artificial intelligence programs, a computer quickly looks for patterns among the proteins that are characteristic of ovarian cancer or other diseases. Five distinct proteins make up the signature of ovarian cancer.
“It’s exactly like an ovarian cancer bar code,” said Dr. Gordon Mills, chief of molecular therapeutics at M.D. Anderson Cancer Center in Houston. “Each one of the bars represents a protein, and depending on where those particular bars are, you can determine the likelihood of whether it’s an ovarian cancer or not.”
Wealth of secrets in blood
Blood contains a lot of information about disease processes going on in the body, but outside of a few tests for specific disorders, this great wealth of information has remained out of reach.
A disease process can make new proteins, modify normal ones, or increase or decrease levels of existing proteins, which are then shed into the bloodstream. Researchers are sifting through millions of potential patterns to identify those that can be used as bar codes for all types of diseases.
“We are using this new technology to mine the hidden protein patterns in blood to determine if they are predictive of biological disease states,” Petricoin said.
Preliminary results from the first of these protein bar codes, ovarian cancer, were reported in the current issue of the British medical journal Lancet.
Because it was early research, the test was used on women already known to have the cancer as a way to measure its accuracy.
It showed that the test was 100 percent accurate in detecting ovarian cancer in women already diagnosed with the disease, including those with stage 1 cancer, the most curable form. With early detection and treatment, 90 percent of women with ovarian cancer are alive after five years. In more advanced cases, only 10 percent of patients are alive five years later.
Among 66 healthy women, the test showed that 63 did not have ovarian cancer, but it gave erroneous results in three cases. If the test were available today, those three false positive patients would be examined with ultrasound or other imaging techniques to either confirm or rule out ovarian cancer, Fishman said.
Early alert for daughters
Elaine Lewin, 74, who beat the bleak odds against surviving ovarian cancer, hopes that the new test under study at Northwestern will put her daughters on track for a sure cure should they develop the same cancer.
Because ovarian cancer tends to run in families, her daughters are at an increased risk, and the tests could give a critical early warning.
Lewin knows the results still have to be verified with further studies, but they are the kind of insurance she hopes will protect her daughters. “My daughters are being watched,” she said. “They are clear right now, and prayerfully they will remain that way. But if there is even a sign of cancer, it would be in the earliest, curable stage.”
Detecting disease conditions that cause changes in the normal chemistry of the body is only the first step, Fishman said. Researchers in his lab are now trying to identify the proteins that are picked up in the protein bar codes to learn what they are doing to cause disease and how they can be turned off.
“We need to understand the enemy,” he said. “How does it feed, how does it grow, what does it need, and then attack it in such a way that we can prevent cancer from occurring.”
Drug therapy for cancer often doesn’t work because cancer is little understood, Fishman said. Once scientists understand how a disease works, it can be treated or prevented, just as the discovery of antibiotics led to an understanding of how infectious germs attack cells and ways to control them.
One of Fishman’s goals is to understand the mechanism by which cancers spread in the body. “This new insight will help us get to the level where we can actually make therapies that are unique and targeted to specific cancer cells,” he said.
