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EDITOR-IN-CHIEF
editorial
William S. Hancock Barnett Institute and Department of Chemistry Northeastern University 360 Huntington Avenue 341 Mugar Bldg. Boston, MA 02115 617-373-4881; Fax: 617-373-2855
[email protected] National Cancer Institute shows the way
ASSOCIATE EDITORS
Joshua LaBaer Harvard Medical School
György Marko-Varga AstraZeneca and Lund University
EDITORIAL ADVISORY BOARD
Ruedi H. Aebersold Institute for Systems Biology
Leigh Anderson Plasma Proteome Institute
Ettore Appella National Cancer Institute
Ronald Beavis University of Chicago
Walter Blackstock Cellzome
Brian Chait The Rockefeller University
Patrick L. Coleman 3M
Catherine Fenselau University of Maryland
Daniel Figeys MDS Proteomics
Sam Hanash University of Michigan
Stanley Hefta Bristol-Myers Squibb
Donald F. Hunt University of Virginia
Barry L. Karger Northeastern University
Daniel C. Liebler Vanderbilt University School of Medicine
Lance Liotta National Cancer Institute
Matthias Mann University of Southern Denmark
Stephen A. Martin Applied Biosystems
Jeremy Nicholson Imperial College of London
Emanuel Petricoin Food and Drug Administration
J. Michael Ramsey Oak Ridge National Laboratory
Pier Giorgio Righetti University of Verona
John T. Stults Biospect, Inc.
Peter Wagner Zyomyx
Keith Williams Proteome Systems
Qi-Chang Xia
n April 22–23, the National Cancer Institute (NCI) assembled a group of leaders from the public and private sectors in proteomic technologies to discuss the challenge of early diagnosis of cancer. It is commendable that NCI is taking the initiative, and rather than wait for proteomics to happen it is attempting to guide proteomic research in the direction of improved molecular profiling of this complex disease. An important goal of this quest for new technologies is to find biomarkers for early cancer detection. Currently, available medical technology is applicable mainly to treatment rather than prevention of cancer, as in many other diseases. To be successful, an early diagnostic test must allow the screening of a large number of individuals who exhibit no disease symptoms. Such a requirement means that the diagnostic test must be relatively noninvasive and involve an easily collected sample, such as plasma. Thus, it is not surprising that characterization of the plasma proteome is a HUPO goal. While plasma is an excellent diagnostic fluid, it is unclear whether cancer markers will appear in plasma, particularly in an early stage of the disease. Thus, NCI has a strong interest in better proteomic technologies, particularly those based on mass spectrometry, which can improve the dynamic range of plasma protein characterization. One would hope that tumor shedding or cell death could result in the release of tumor markers into plasma, but detection would require a sensitive assay such as ELISA. After characterization of the appropriate markers, other technologies will come into play, such as the development of a protein array, which could allow the rapid screening of a number of markers related to a range of cancers. For mass screening, the requirements for such a test are very high, as the health care system cannot tolerate false positives or negatives except at a very low level. Therefore, much of this technology session concentrated on strategies toward validation of cancer detection platforms so that research in this field does not remain at an academic level, but can be applied in the clinical arena. In this context, NCI is working closely with FDA so that research is carried out with an understanding of the regulatory requirements for a new clinical device. The difficulty in obtaining appropriate clinical samples and collecting appropriate controls were two major concerns of the meeting. In the development of cancer markers, it is helpful to perform tumor tissue analysis as well as analyze matched blood samples. In both cases there are many issues around appropriate collection and preservation protocols, as nonspecific proteolysis of the sample is likely. Some tumors are associated with the release of metalloproteases, and in such cases proteins in the sample could be more rapidly degraded than in a normal sample. Another concern is the detection of posttranslational modifications, particularly in a high-throughput manner. Cancer is often associated with changes in glycosylation as well as phosphorylation, so it may be necessary to quantitate changes in such modifications, as well as protein expression levels. Research is also necessary in bioinformatics for the analysis of large data sets, and substantial resources will need to be allocated to such efforts. In conclusion, one can see that NCI was farsighted in organizing such a meeting. There will need to be follow-up to guide development of appropriate platforms, the planning of clinical trials, and the collection and assessment of data. While there is not a simple platform at the present time that will provide a solution to the NCI challenge, one can see that the technology is rapidly evolving and some solutions are currently available. It is an exciting prospect that proteomics could make a difference in the diagnosis and treatment of such a public and high-impact disease, and we await future developments with excitement.
O
Shanghai Institute of Biochemistry
John R.Yates, III The Scripps Research Institute
© 2003 American Chemical Society
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