Alliance of Glycobiologists for Detection of Cancer and Cancer Risk Fact Sheet
What is the Alliance of Glycobiologists for Detection of Cancer and Cancer Risk?
The Alliance is a trans-National Institutes of Health initiative to discover and develop new classes of molecular markers that can be used to detect cancer early. This effort seeks to discover, develop, and clinically validate cancer biomarkers by targeting complex carbohydrates, or the "glycan," part of a molecule.
Biomarkers are substances that can be found in the blood, other body fluids, or tissues, and used to measure informative biological processes. In addition to genes and proteins, they can be complex carbohydrate (sugar) structures that are attached to protein and lipid (fat) molecules.
Seven NCI-Supported Tumor Glycomics Laboratories make up the primary component of the Alliance. The Consortium for Functional Glycomics (CFG), funded by the National Institute of General Medical Sciences (NIGMS), Glycomics and Glycotechnology Resource Centers funded by the National Center for Research Resources (NCRR) and NCI's Early Detection Research Network (EDRN) are the partnering components.
Why was the Alliance created?
Glycomic biomarkers based on the carbohydrate portion of a glycoprotein represent a largely untapped arena relevant to cancer detection and diagnosis. The goal of this program is to identify clinically-relevant glycans that can enhance diagnostic performance, either alone or in combination with existing markers. Since no single institution or individual has the resources or expertise to expand the existing knowledge of glycobiology in relation to cancer, NCI in 2007 launched the Alliance of Glycobiologists for Detection of Cancer and Cancer Risk to bring together groups and individuals in a focused endeavor.
What are glycans?
Glycans are sugars that are linked together, often forming complex branched-chain structures, and which are bound to proteins and lipids. Glycans dominate the surfaces of cells and are known to mediate many biological processes. (See the photo and caption below.) Humans are believed to synthesize thousands of glycan structures. While there are about 7,000 known structures, their significance in diagnosis and treatment is yet to be fully established. Glycans are extremely abundant, but recent advances in technology have only now allowed a systematic study of them. Many current cancer biomarkers are glycoproteins, but little effort has been taken to exploit their glycan structures to improve diagnostic performance.
This electron micrograph illustrates how sugars dominate the surfaces of cells. It shows a section of a kidney tubule magnified 125,000 times with cellular processes that line the exterior wall of a capillary. Staining was performed with an agent to bind the carbohydrate-rich surface of the cellular processes visible as dark spots (pointed out by arrows). The dark region is known as the glycocalyx of the cell.
Courtesy of Dr. Peter Andrews, Department of Biochemistry, Molecular and Cellular Biology, Georgetown University, School of Medicine.
What is glycomics?
Glycomics is a field that overlaps proteomics in covering certain post-translational modifications (PTMs) of proteins. Glycomics is quickly becoming a driving force for discovering potential cancer biomarkers. Changes in PTMs often result in pathophysiologic conditions, and underpin the multitude of potential biomarkers associated with proteins.
Recent evidence suggests that cancers may always display alterations in glycan structures attached to proteins. Numerous studies comparing normal and tumor cells have shown that changes in the glycan structures of cells correlate with cancer development. Many protein biomarkers also have glycan components and analysis of these two molecular structures together may improve the value of other existing tests.
What does the Alliance do?
The NCI-funded Tumor Glycomics Laboratories are searching for glycan-based biomarkers for detecting breast, ovarian, lung, prostate, colon, and pancreatic cancers, and collaborating with other programs seeking cancer biomarkers. In working with NCI's Early Detection Research Network (EDRN), the Alliance brings together centers of expertise in tumor biology, diagnostic technologies, and clinical trial methodologies from academia, industry, and government.
Specifically, the Alliance is working to:
- Identify oligosaccharide-based biomarkers specific to defined tumors that can be used for early detection, diagnosis, or prognosis;
- Develop and apply glycan arrays for cancer biomarker discovery, validation and screening; and
- Develop and validate additional tools and reagents to enable high-throughput testing of glycomic biomarkers.
The Alliance is managed by a centralized Coordination Unit comprised of the principal investigators of the laboratories, representatives from the CFG and EDRN, and NIH program staff from NCI, NCCR and NIGMS.
Who are the members of the Alliance and what are their project areas?
The Tumor Glycomics Laboratories are listed below in alphabetical order by the principal investigator. They offer varied expertise and technologies. More information is available via the links below.
- William Hancock, Ph.D., Sc.D.
Northeastern University, Boston, MA
Laboratory Project: Glycan markers for the early detection of breast cancer
- Michael Hollingsworth, Ph.D.
University of Nebraska, Omaha, NE
Laboratory Project: Autoantibodies against glycopeptide epitopes as serum biomarkers of cancer
- Margaret Huflejt, Ph.D.
New York University, New York, NY
Laboratory Project: Discovery and clinical validation of cancer biomarkers using printed glycan array
- Milos Novotny, Ph.D.
Indiana University, Bloomington, IN
Laboratory Project: Early cancer detection and prognosis through glycomics
- J. Michael Pierce, Ph.D.
University of Georgia, Athens, GA
Laboratory Project: Tumor glycomics laboratory for discovery of pancreatic cancer markers
- Ajit Varki, M.D.
University of California San Diego, San Diego, CA
Laboratory Project: Neu5Gc and Anti-Neu5Gc antibodies for detection of cancer and cancer risk
- Denong Wang, M.D., Ph.D.
SRI International (formerly Stanford Research Institute) Menlo Park, CA
Laboratory Project: Immunogenic sugar moieties of prostate cancers
How do the partnering groups work with the Alliance?
The CFG (www.functionalglycomics.org) and several Glycomics and Glycotechnology Resource Centers (www.ncrr.nih.gov/Glycomics) partner with the Tumor Glycomics Laboratories. For example, the Tumor Glycomics Laboratories can seek help with technical analysis of glycan profiles, access to glycan or "glyco-gene arrays", or obtain specific reagents and products. CFG offers many of the unique core resources that are specific to glycomics.
The EDRN (edrn.nci.nih.gov), an NCI-funded consortium that promotes clinical validation of cancer biomarkers for early detection and cancer risk, will help the Alliance to validate glycomic cancer biomarkers. EDRN provides support for study design, statistical analysis, patient accrual, and collection of clinical specimens. EDRN also provides access to specifically designed reference sets (usually serum or plasma) for various cancers.
The Alliance collaborates with groups such as the Human Proteome Organization (www.hupo.org), through informal and formal arrangements, and with other NCI programs when needs arise, to derive maximum benefits from existing resources in the field.
Structure of Alliance
What are the scientific objectives of the Alliance?
Objectives of the Alliance are:
- To support and facilitate a broad spectrum of research activities that identify cancer-related abnormalities associated with glycoconjugates having the potential to serve as cancer biomarkers. These research activities will involve a progression typified by: (a) the use of a variety of platforms and technologies for discovery of specific glycans or characteristics of glycan profiles that correlate with defined cancers; (b) the performance evaluation in terms of sensitivity and specificity of these biomarker candidates in case versus control clinical specimens; and (c) culmination in translational efforts to test the most promising biomarker candidates in clinical validation studies.
- To place highest priority on biomarkers for early detection and primary prevention of cancer, however, markers for diagnostic clinical testing of cancer or stratification of cancer risk also fulfill the mission of the Alliance . It is possible that markers for prognosis or prediction of response to therapy may arise from this research, and where appropriate, these additional biomarker applications will be explored.
- To function as a highly collaborative consortium facilitating cancer glycan biomarker discovery and development. Collaboration will be fostered through open discussion of research developments and discussions of strategies to most efficiently interrogate complex carbohydrates of clinical significance.
- To contribute to the development of glycan structural databases maintained by the Consortium for Functional Glycomics (CFG). All new structures elucidated from efforts supported by Alliance funding will be deposited into CFG databases.
- To promote collaboration and communication with other relevant programs at the NCI, other Institutes within NIH, and academic and industrial leaders where the research interests coincide with the mission of the Alliance.
For more information, see the following:
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