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New Initiative to Study the Glycobiology of Cancer Could Aid Understanding of Cancer Risk and Detection

  • Posted: August 22, 2007

The National Cancer Institute (NCI), part of the National Institutes of Health (NIH), is funding a new $15.5 million, five-year initiative to discover, develop, and clinically validate cancer biomarkers by targeting the carbohydrate (glycan) part of a molecule.  Biomarkers are substances sometimes found in the blood, other body fluids, or tissues that measure biological processes, and in addition to genes and proteins, can be complex carbohydrate (sugar) structures that are attached to protein and lipid (fat) molecules.  Seven NCI-funded Tumor Glycome Laboratories are now searching for glycan-based biomarkers for melanoma, and breast, ovarian, lung, prostate, colon, and pancreatic cancers.

“Scientists have long recognized that certain sugar structures, which are attached to protein and lipid molecules, may be important as markers for cancer development,” said NCI Director John E. Niederhuber, M.D. “While this area has compelling scientific interest, its biological and chemical complexities have often discouraged investigation. Today, with the advent of advanced technologies to conduct protein and carbohydrate chemistry, research into this intriguing area has experienced renewed interest.

Numerous studies comparing normal and tumor cells have shown that changes in the glycan structures of cells correlate with cancer development. Glycans are extremely abundant, but recent advances in technology have only now allowed a systematic study of these structures. Many protein biomarkers also have glycan components and analysis of these two molecular structures together may improve the value of tests such as those for prostate-specific antigen (PSA), CA-125, and carcinoembryonic antigen, which are sometimes used in prostate, ovarian, and colon cancer detection, respectively.

The NCI’s Tumor Glycome Laboratories are the principle component of the new trans-NIH Alliance of Glycobiologists for Detection of Cancer and Cancer Risk.  The other components of the alliance are the Consortium for Functional Glycomics funded by the National Institute of General Medical Sciences and several Glycomics and Glycotechnology Resource Centers supported by the National Center for Research Resources.  The NCI’s Early Detection Research Network (EDRN) is also an alliance member, providing support for design and statistical analysis, patient accrual, and collection of clinical specimens to facilitate validation studies using EDRN’s existing components.

“Looking at different types of biomarkers and new ways to identify them is critically important to both the basic understanding of cancer and the ability to identify early cancer and risk for cancer,” said Sudhir Srivastava, Ph.D., chief of the Biomarkers Research Group in NCI’s Division of Cancer Prevention.  “We believe this new Alliance of Glycobiologists will accelerate the pace of biomarker development and discovery.”

The project is headed by Karl Krueger, Ph.D., a program director in the Biomarkers Research Group in NCI’s Division of Cancer Prevention.

The seven Tumor Glycome Laboratories projects funded by NCI are:

Project Title
Principal Investigator
Institution

Objectives of Project
Cancer Type Under Study

Discovery and clinical validation of cancer biomarkers using printed glycan array

Margaret Huflejt, Ph.D.
New York University
New York, NY

Determine the diagnostic or prognostic anti-glycan auto-antibody signatures in patients. For breast cancer, determine how many years prior to diagnosis that progression to cancer can be predicted.

Breast, Ovary, Lung, Melanoma

Immunogenic sugar moieties of prostate cancers

Denong Wang, M.D., Ph.D.
Stanford Research Institute
Palo Alto, Calif.

Identify anti-glycan autoantibody signatures in prostate cancer patients.

Prostate

Early cancer detection and prognosis through glycomics

Milos Novotny, Ph.D.
Indiana University
Bloomington, Ind.

Identify biomarkers from glycans released from serum glycoproteins and develop high-throughput platforms to measure biomarkers suitable for the clinic.

Prostate, Ovary, Lung, Colon

Glycan markers for the early detection of breast cancer

William Hancock, Ph.D., Sc.D.
Northeastern University
Boston, Mass.

Identify breast cancer biomarkers based on aberrant glycan modifications on defined amino acid residues of serum glycoproteins

Breast

Tumor glycomics laboratory for discovery of pancreatic cancer markers

J. Michael Pierce, Ph.D.
University of Georgia
Athens, Ga.

Identify glycoprotein and glycolipid biomarkers for pancreatic cancer in pancreatic ductal fluid that can also be found in serum. Develop assays for promising biomarkers.

Pancreas

Autoantibodies against glycopeptide epitopes as serum biomarkers of cancer
 
Michael Hollingsworth, Ph.D.
University of Nebraska
Lincoln, Neb.

Determine auto-antibody signatures to mucin glycopeptides in pancreatic and breast cancer patients.
 
Pancreas, Breast

Neu5Gc and Anti-Neu5Gc antibodies for detection of cancer and cancer risk

Ajit Varki, M.D.
University of California San Diego
San Diego, Calif.

Expand on research showing that cancer patients express cell surface glycans containing the sialic acid N-glycolylneuraminic Acid (Neu5Gc) and produce autoantibodies to these structures.

Lung, Pancreas, Ovary

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For more information on the Tumor Glycome Laboratories and the NIH Alliance of Glycobiologists for Detection of Cancer and Cancer risk, visit:

For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).