Fred Hutchinson receives $9.7 million to lead early detection consortium

December 13, 2004

SEATTLE - The National Cancer Institute (NCI), part of the National Institutes of Health, has announced that SAIC-Frederick Inc.* has made two-year awards, under a competitive solicitation, totaling $13.4 million to two research teams from 10 cancer-research institutions. Scientists from Fred Hutchinson Cancer Research Center will lead one of the research teams; scientists from the University of Michigan Medical School in Ann Arbor will lead the other team.

Fred Hutchinson was awarded $9.7 million to lead a research consortium dedicated to developing simple blood tests to detect the earliest signs of cancer and other diseases so they can be treated as early as possible, when cure rates are highest.

Collaborating institutions include the Institute for Systems Biology in Seattle, Pacific Northwest National Laboratories in Richland, Wash., and the Plasma Proteome Institute in Washington, D.C.

The initial aim of the National Cancer Institute-funded consortium is to identify serum biomarkers - proteins in the blood that either alone or in combination are detected in altered amounts in people with cancer or who are at high risk of developing the disease.

The ultimate goal of the consortium is to create highly reliable and inexpensive biomarker-based blood tests that could identify the onset and risk of a wide range of cancers and other diseases so they could be prevented or treated at the earliest possible stage.

The strong history of collaboration among the participating institutions and researchers - all major contributors to the field of biomarker discovery - was key to getting the grant, said Martin McIntosh, Ph.D., principal investigator of the award and an early detection researcher in Fred Hutchinson's Public Health Sciences Division.

"All of the institutions involved are international leaders in the rapidly advancing field of proteomics, which attempts to catalog and describe the function of all of the proteins made by a cell or organism," he said. "Together we aim to create a platform for biomarker discovery and analysis that could be used by collaborators around the world."

The first year of the two-year award will be devoted to developing and refining the technology needed to compare approaches for discovering new biomarkers and making sure they are reliable and accurate signposts of disease. The second year will focus on testing the technology's ability to detect diagnostic protein biomarkers that are associated with several different mouse models of human cancer, including those of the breast, prostate, ovary, pancreas, skin and lung.

The researchers have their work cut out for them. Although the entire human genome contains only about 30,000 genes, the number of predicted protein forms approaches 1 million. So far, less than 1 percent of the proteins have been detected in serum.

The quest to identify and analyze protein patterns in the blood - the focus of a relatively new field called proteomics - involves extracting proteins from blood, urine or other tissue. The proteins are then analyzed with a technique called mass spectrometry, which creates patterns of protein fragments. These unique protein signatures are then sorted with an artificial-intelligence computer program that identifies the discrepancies in protein patterns between people with and without cancer. Proteins linked to cancer may then serve as biomarkers to detect early disease and predict responsiveness to therapy or the likelihood of recurrence. Such biomarkers also could be used to classify the genetic subtype of the cancer so that treatment could be better tailored to the individual.

Geneticist and clinical oncologist Amanda Paulovich, M.D., Ph.D., of Fred Hutchinson's Clinical Research Division, is co-principal investigator of the award. Her work focuses on developing blood-based breast-cancer screening tests.

"If cancer is detected when it is still localized, we can cure it virtually 100 percent of the time with surgery and targeted radiotherapy," she said. "Once it has spread, it requires chemotherapy and becomes much harder to treat successfully."

For example, solid tumors can be cured 90 percent of the time if they're detected and treated early, whereas cure rates for late-stage cancer are usually only about 10 percent.

Fred Hutchinson was selected to lead the consortium, McIntosh said, because it can provide the expertise and infrastructure necessary for moving the results of new proteomic technologies from the laboratory into the clinic.

" Once we determine how to systematically discover those markers characteristic of early cancer development, the next challenge will be to go out and conduct population-based studies to find out if using them clinically can save lives. Fred Hutchinson Cancer Research Center has been a leader in that aspect of early detection as well," McIntosh said The recent award - a key part of Fred Hutchinson's Early Detection and Intervention Initiative launched last year through $4.4 million in private funding - represents the latest in a series of major biomarker-research funding grants to institutions within the new consortium, underscoring their stature in the field of proteomics.

Last year, for example, the Pacific Northwest National Laboratory received $10.2 million from the National Institutes of Health to develop advanced instrumentation for studying large and complex protein sets, thus establishing PNNL as a worldwide base for proteomics research. In 2002, the Institute for Systems Biology received $19.8 million from the National Heart, Lung and Blood Institute to establish one of 10 NHLBI Proteome Research Centers in the nation.

CONSORTIUM LEADERSHIP

Fred Hutchinson Cancer Research Center - Seattle, Wash.
Principal investigator Martin McIntosh, Ph.D., is an associate member of Fred Hutchinson's Public Health Sciences Division and research associate professor of biostatistics at the University of Washington. McIntosh will lead the project's informatics-development team at Fred Hutchinson and coordinate informatics work across the consortium, including study design and analysis and the development of algorithims, or mathematical tools, for data analysis.

McIntosh is known internationally for his expertise in discovering and evaluating novel biomarkers for use in the early detection of cancer, particularly cancers of the ovary, breast and cervix. His group uses proteomics to evaluate how blood proteins behave over time in women with ovarian cancer as compared to healthy women at normal risk and healthy women whose risk is elevated due to inherited mutations in the BRCA1 or BRCA2 genes. This research may help tailor biomarkers to specific risk groups and identify which biomarkers best indicate the subtle biological changes associated with early cancer development.

Co-principal investigator Amanda Paulovich, M.D., Ph.D., an assistant member of Fred Hutchinson's Clinical Research Division, is a geneticist and clinical oncologist. She will supervise personnel and coordinate experimental work across all sites of the consortium. She'll also be involved in study design across all participating institutions.

Her work focuses on finding biomarkers of cancer risk. For example, Paulovich and her colleagues are working to develop a reliable blood test that can pick out women with subtle, inherited genetic risk factors that put them at higher risk for breast cancer. Specifically, the test would screen for proteins that signal genetic defects associated with faulty DNA repair. Women who harbor such genetic mutations would be good candidates to receive more intensive screening for breast cancer.

Project co-investigator Christopher Kemp, Ph.D., an associate member of Fred Hutchinson's Human Biology and Public Health Sciences divisions, will coordinate all mouse-model work, including the importation of mice from the NCI's Mouse Model Consortium, which will provide strains of mice and plasma samples for biomarker discovery. Kemp, also an affiliate associate professor of pathology at the University of Washington, focuses on using mouse models of human cancer to understand how environmental exposure to carcinogens interact with genes to cause cancer.

COLLABORATING INSTITUTIONS AND RESEARCHERS

The Institute for Systems Biology - Seattle, Wash.
Researchers at ISB have developed novel technologies for processing blood that allow a large number of proteins to be observed. In addition to providing these key technologies, the institute will lend its expertise in designing mathematical tools and software for data analysis. ISB founding member Ruedi Aebersold, Ph.D., and senior research scientist Julian Watts, Ph.D., will oversee this effort. Pacific Northwest National Laboratory - Richland, Wash.

Researchers at PNNL, a world leader in the development of protein-separation technologies, will contribute a large suite of complex data-analysis tools and also will use their novel instrumentation to survey and identify a large number of blood proteins. Richard D. Smith, Ph.D., Batelle Fellow and chief scientist of the Biological Sciences Division and Environmental Molecular Sciences Laboratory, will oversee this effort.

Plasma Proteome Institute - Washington, D.C.
Researchers at PPI will provide validation of candidate biomarkers discovered by the consortium and will use bioinformatics methods to create a database of proteins known to be important in tumor formation and growth. Leigh Anderson, Ph.D., chief executive officer of PPI, will oversee this effort.

Other collaborators on the project include Eric Lander, Ph.D., director of the Eli and Edythe L. Broad Institute at the Massachusetts Institute of Technology. Lander, one of the leaders of the Human Genome Project, will consult on a number of issues regarding proteomic analysis, including the creation of a public-use database.
-end-
ABOUT THE PARTICIPATING INSTITUTIONS

Fred Hutchinson Cancer Research Center - Fred Hutchinson Cancer Research Center, home of three Nobel laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical research to eliminate cancer and other potentially fatal diseases. Fred Hutchinson, located in Seattle, Wash., receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, UW Medicine and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 40 nationwide. For more information, visit the center's Web site at www.fhcrc.org. Advancing Knowledge, Saving Lives

Institute for Systems Biology - The Institute for Systems Biology (ISB) is an internationally renowned nonprofit research institute dedicated to the study and application of systems biology. ISB's goal is to unravel the mysteries of human biology and identify strategies for predicting and preventing diseases such as cancer, arthritis and AIDS. The driving force behind the innovative "systems" approach is the integration of biology, computation, and technology. This approach allows scientists to analyze all of the elements in a system rather than one gene or protein at a time. Located in Seattle, Wash., the Institute has grown to more than 170 faculty and staff members; has been awarded almost $130 million in funding; and has an extensive network of academic and industrial partners. For more information, contact: www.systemsbiology.org. Revolutionizing Science. Enhancing Life.

Pacific Northwest National Laboratory - The Pacific Northwest National Laboratory is a Department of Energy Office of Science research facility that advances the fundamental understanding of complex systems and provides science-based solutions to some of the nation's most pressing challenges in national security, energy and environmental quality. In the biotechnology and health sciences, focus areas include research in molecular and cell biology, basic and applied toxicology, computational biology and technology development. The laboratory, with its main campus located in Richland, Wash., employs more than 3,800 scientists, engineers, technicians and support staff, and has an annual budget of nearly $600 million. Battelle, based in Columbus, Ohio, has operated PNNL for the federal government since 1965. For more information, visit www.pnl.gov.

Plasma Proteome Institute - The Plasma Proteome Institute (PPI) is a private nonprofit institution located in Washington, D.C. PPI is working to promote the exploration and diagnostic use of the plasma proteome as a means to better detect, understand and treat disease. PPI cooperates with researchers, institutions and companies interested in the pursuit of plasma proteome science. For more information, visit www.plasmaproteome.org

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*SAIC (Science Applications International Corporation)-Frederick is the operations and technical support contractor for the NCI in Frederick, Md., operating the NCI-Frederick campus.

Fred Hutchinson Cancer Research Center

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