Molecular fingerprints  pg. 6

“Ovarian cancer is ripe for using this technique because it is usually diagnosed too late, when it’s almost untreatable, whereas if you catch it early enough, surgery alone can cure this disease most of the time,” Petricoin says.

Using a similar technique, researchers at Eastern Virginia Medical School in Norfolk have identified a pattern of nine serum proteins that accurately distinguish between prostate cancer, benign prostate hyperplasia (non-cancerous enlargement of the prostate gland), and healthy tissue.

The technique was considerably more specific than the PSA test, which has a high rate of false positive results, the researchers reported in 2002. If validated by further study, “this approach would have immediate and substantial benefit in reducing the number of unnecessary biopsies,” they concluded.

Caprioli and his colleagues have developed another mass spectrometry technique, called “imaging mass spectrometry,” that can actually “look” inside the tumor itself.

Using a laser and high-speed electronics and computers, they modified standard spectrometers so they could generate digital pictures, showing the distribution of individual proteins in cells and tissues. In April 2001 the researchers reported finding high levels of thymosin beta-4, a protein that may be a harbinger of malignant growth, in the outermost, proliferating edge of a human brain tumor that had been implanted in a mouse.

These “molecular photographs” may help improve the diagnosis and treatment of cancer. By pinpointing the precise location in the tissue where high levels of a protein are spurring cancerous growth, the technique could improve the accuracy of cancer surgery.

Repeat studies also can help determine how quickly tumors are growing, and whether they are responding to drug treatment, Caprioli says. This is “molecular insight that can be directly applied to patient care,” he says.

Petricoin acknowledges criticism that he and his colleagues have not identified the proteins they’re picking up in the blood. That will be crucial, other scientists say, for understanding the role the proteins may play in cancer growth, and how to develop new drugs to stop them. That’s true, agrees Petricoin, but patients need this technology now.

“We’re failing in the war against cancer,” he told a group of researchers at Vanderbilt in 2002. “For patients who have ovarian cancer … who have seen their mothers die of cancer, they don’t care what the underlying identity (of the protein) is. We have to test this hypothesis in the clinic. (But) we could use that pattern as a diagnostic today.”

Discovery science

“I don’t think they (the ‘omic’ strategies) will provide the answers to all of life’s mysteries,” responds Walter Chazin, Ph.D., Chancellor's Professor of Biochemistry and Physics and director of the Center for Structural Biology at Vanderbilt. “Nothing significant has been achieved yet … from using proteomics. It’s really in the technical development stage. The more we learn, the more complex it becomes.

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