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NCI has launched a new initiative to determine whether carbohydrates can be used as biological markers for detecting cancer and assessing disease risk. The $15.6 million, 5-year initiative will complement efforts to identify gene and protein biomarkers by focusing on an important, if understudied, class of molecules.

Like genes and proteins, complex carbohydrates - also known as glycans - may be altered as cancer develops. The goal of the new initiative is to identify panels of glycan-based biomarkers associated with early-stage cancers and validate the panels in clinical samples.

"Glycans represent one of the richest sources of potential cancer biomarkers," says Dr. Karl Krueger of NCI's Division of Cancer Prevention (DCP), who heads the project, called the Alliance of Glycobiologists for Detection of Cancer and Cancer Risk.

Glycans are sugars that are linked together, often forming complex branched-chain structures, and are bound to proteins and lipids, modifying the behavior of these molecules. Glycans have dominated the surfaces of cells for billions of years and are widely thought to mediate many biological processes.

One of the most promising cancer biomarkers in development today is a "glycoprotein" known as GP73. This marker for liver cancer is expected to undergo validation testing through NCI's Early Detection Research Network (EDRN) in the coming months.

EDRN is providing Alliance researchers with expertise on the critical process of validation, where many promising potential biomarkers have failed.

The trans-NIH Alliance includes the Consortium for Functional Glycomics, funded by the National Institute of General Medical Sciences (NIGMS), and several Glycomics and Glycotechnology Resource Centers supported by the National Center for Research Resources (NCRR).

Glycans are structurally more complex than DNA or proteins, and this has slowed efforts to study the molecules on a large scale. But recent advances in technologies, such as the development of glycan arrays, have made the initiative feasible.

"The core technologies are in place and this means that researchers can focus on discovering biomarkers rather than building infrastructure," says Dr. Sudhir Srivastava, head of NCI's Cancer Biomarkers Research Group, which is sponsoring the initiative.

The initiative is a critical piece of NCI's efforts in biomarker development, adds Dr. Srivastava. "Traditional methods of analyzing DNA and proteins cannot detect cancer-related changes involving glycans," he notes.

Information about glycans could improve the utility of protein-based biomarkers in use today, including prostate-specific antigen for prostate cancer and CA-125 for ovarian cancer. Both proteins have glycan components, and analyzing their molecular features together may yield useful information for physicians and patients, the researchers say.

Alliance members came to NCI for a kick-off meeting last week. It was the first time that glycobiologists had come together in one room with the goal of applying the field's new technologies and insights to the challenge of detecting cancer biomarkers.

If the initiative succeeds, several participants said, interest in glycobiology will grow and carbohydrates just might emerge from the shadow of genes and proteins.