Molecular fingerprints  pg. 4

Different parts of the body have different populations of proteins. They change, too, in response to environmental influences, like the digestion of a piece of cherry pie—or even the time of day. “Your proteins won’t be the same tonight as they are now,” says Richard Caprioli, Ph.D., director of the Mass Spectrometry Research Center at Vanderbilt.

Proteins aren’t lone wolves, either. They act and react as part of intricate networks and pathways that transmit signals to and from the DNA, across the cell membrane and through the blood to distant parts of the body. Thus, proteins have been called “molecular machines,” at work in cellular “factories.”

Just as proteins carry out many of the functions necessary for life, they also are at the root of many diseases. A form of diabetes, for example, results from an inadequate supply of insulin.

A change in a single amino acid in the oxygen-transporting hemoglobin molecule alters the protein’s three-dimensional shape, and results in sickle-cell anemia. Red blood cells with the abnormal protein are misshapen (sickle-shaped), break apart and block small blood vessels, causing pain and low blood count (anemia).

Too much protein also can be a problem. Elevated levels of the receptor for epidermal growth factor, for example, has been linked to a variety of cancers.

Molecular fingerprints

This connection between proteins and cancer, in particular, is driving a new growth industry in proteomics. Much of the effort is aimed at developing new drugs targeting specific proteins. But the search for new diagnostics is equally intense. That’s because some diseases, including some forms of cancer, typically escape notice until they are in an advanced, hard-to-treat stage.

Currently cancer is diagnosed through a variety of techniques, both non-invasive (ultrasound, X-rays, CAT scans, etc.) and invasive (primarily surgery). There are a few blood tests for cancer, which detect cancer-related antigens (proteins that bind with antibodies), but these are far from definitive.

For example, prostate cancer is associated with increased levels of prostate-specific antigen (PSA), but PSA levels also rise in response to exercise, infection and certain medications. Levels of cancer antigen 125, a screening tool for ovarian cancer, are abnormally high only about half the time in early disease.

Several years ago, researchers at the U.S. Food and Drug Administration and National Cancer Institute joined forces in an attempt to improve early detection of cancer, determine in advance which treatments are likely to be most successful in individual patients and, ultimately, to develop new “targeted” therapies that effectively stop cancer growth without harming normal tissue.

“Certainly cancer is underpinned by genomic disorders but functionally it’s a proteomic disease,” says Emanuel Petricoin, Ph.D., the project’s lead FDA researcher. “Effectively it’s the rewiring and miswiring of the protein circuits, the signal pathways, that cause cells to grow and not die.”

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