The major objective of the Alliance is to discover and develop molecular markers for early detection of cancer by conducting innovative, translational research in the field of complex carbohydrates. An important key to biomarker discovery is to understand the biological mechanisms by which changes in glycosylation promote cancer progression. Taking this biologically-informed approach, Alliance investigators focus their efforts on specific classes of glycan markers that are likely to play important roles in oncogenesis.
The eight NCI-supported Tumor Glycomics Laboratories cover most forms of glycans produced by human cells including N- and O-glycoproteins, glycolipids, glycosaminoglycans, and GPI-anchored proteins. The laboratories use a variety of platforms and technologies to achieve the following objectives:
- Develop hypothesis-driven approaches to biomarker discovery by addressing aspects of tumor glycobiology promoting oncogenic cellular behavior such as stimulated cell growth, inhibition of programmed cell death, loss of adhesion, metastasis, and invasion;
- Identify cancer-related abnormalities associated with glycoconjugates that have the potential to serve as cancer biomarkers;
- Place highest priority on biomarkers for early detection and prevention of cancer, however, markers for diagnostic clinical testing of cancer or stratification of cancer risk also fulfill the mission of the Alliance;
- Function as a highly collaborative consortium facilitating cancer glycan biomarker discovery and development;
- Contribute to the development of glycan structural databases maintained by the Consortium for Functional Glycomics; and
- Promote collaboration and communication with other relevant programs at NCI, other Institutes within NIH, and academic and industrial leaders where the research interests coincide with the mission of the Alliance.
Toward these goals, each laboratory has assembled components to address biomarker discovery, carbohydrate analysis, clinical specimens, and statistical support. Together the Alliance is pursuing such research matters as: glycan structural analysis, glycan profile comparisons, glycan and lectin array technologies, carbohydrate-specific monoclonal antibodies, recombinant lectins, glycosyltransferase expression, genomic analysis of glycosylation-related genes, and glycan biomarkers derived from body fluids, tumor samples, or human tumor cell lines.
The laboratories conduct open discussions of research developments and strategies to efficiently interrogate complex carbohydrates of clinical significance. All new structures elucidated from the Alliance's efforts are deposited into databases maintained by the Consortium for Functional Glycomics,Specific resource needs such as access to special technologies, glycoenzymes, glycan arrays, reagents, and defined glycan standards of high purity are available through several programs and initiatives supported by the National Institute of General Medical Sciences (NIGMS) and National Heart, Lung, and Blood Institute (NHLBI). Logistical support for clinical validation of biomarkers is promoted through the Early Detection Research Network.
Members of the Alliance's Steering Committee (SC) oversee and coordinate activities. They review data; offer recommendations on strategies to expedite biomarker progression to validation status; determine when specific biomarker studies are ready for larger scale clinical validation; and monitor study results.