|New Initiative to Study the Glycobiology of
Cancer Could Aid Understanding of Cancer Risk and Detection
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
“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
“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:
|Objectives of Project
Cancer Type Under Study
|Discovery and clinical validation
of cancer biomarkers using printed glycan array
Margaret Huflejt, Ph.D.
La Jolla, Calif.
|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.
Palo Alto, Calif.
|Identify anti-glycan autoantibody signatures
in prostate cancer patients.
|Early cancer detection and
prognosis through glycomics
Milos Novotny, Ph.D.
|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.
|Identify breast cancer biomarkers based on aberrant
glycan modifications on defined amino acid residues of serum
|Tumor glycomics laboratory
for discovery of pancreatic cancer markers
J. Michael Pierce, Ph.D.
University of Georgia
|Identify glycoprotein and glycolipid biomarkers
for pancreatic cancer in pancreatic ductal fluid that can also
be found in serum. Develop assays for promising biomarkers.
|Autoantibodies against glycopeptide
epitopes as serum biomarkers of cancer
Michael Hollingsworth, Ph.D.
University of Nebraska
|Determine auto-antibody signatures to mucin
glycopeptides in pancreatic and breast cancer patients.
|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
For more information on the Tumor Glycome Laboratories and the
NIH Alliance of Glycobiologists for Detection of Cancer and Cancer
For more information about cancer, please 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).
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.