E ditor - in - chief
William S. Hancock
editorial
Barnett Institute and Department of Chemistry Northeastern University Boston, MA 02115 617-373-4881; fax 617-373-2855
[email protected] Associate E ditors Joshua LaBaer Harvard Medical School György Marko-Varga AstraZeneca and Lund University Martin McIntosh Fred Hutchinson Cancer Research Center Cons u lting E ditor Jeremy K. Nicholson Imperial College London E ditorial adv isory board Ruedi H. Aebersold ETH Hönggerberg Leigh Anderson Plasma Proteome Institute Rolf Apweiler European Bioinformatics Institute Ronald Beavis Manitoba Centre for Proteomics John J. M. Bergeron McGill University Rainer Bischoff University of Groningen Richard Caprioli Vanderbilt University School of Medicine R. Graham Cooks Purdue University Thomas E. Fehniger AstraZeneca Catherine Fenselau University of Maryland Daniel Figeys University of Ottawa Sam Hanash Fred Hutchinson Cancer Research Center Stanley Hefta Bristol-Myers Squibb Denis Hochstrasser University of Geneva Michael J. Hubbard University of Melbourne Donald F. Hunt University of Virginia Barry L. Karger Northeastern University Joachim Klose Charité-University Medicine Berlin Matthias Mann Max Planck Institute of Biochemistry David Muddiman North Carolina State University Robert F. Murphy Carnegie Mellon University Gilbert S. Omenn University of Michigan Akhilesh Pandey Johns Hopkins University Aran Paulus Bio-Rad Laboratories Jasna Peter-Katalini´c University of Muenster Peipei Ping University of California, Los Angeles Henry Rodriguez National Cancer Institute Michael Snyder Yale University Clifford H. Spiegelman Texas A&M University Ruth VanBogelen Pfizer Global Research & Development Timothy D. Veenstra SAIC-Frederick, National Cancer Institute Scot R. Weinberger GenNext Technologies Susan T. Weintraub University of Texas Health Science Center John R. Yates, III The Scripps Research Institute
It Takes a Village To Develop Biomarkers
A
lthough much has been written about the promise of proteomics for biomarker discovery, much has also been written about the paucity of protein biomarkers that have reached the stage of U.S. Food and Drug Administration approval. This situation is not surprising given the following facts. 1. The discovery process often has been undertaken in an isolated laboratory with the use of customized platforms and limited means to progress from the discovery stage to validation. 2. We are the victims of our own success. The sheer number of candidate biomarkers creates an impediment to further development, because those markers that have the greatest potential are not recognized easily. Diagnostic companies therefore face the dilemma of which markers to invest in and often require that markers have reached an advanced stage of validation and assay optimization before getting involved. 3. When discovered markers are scrutinized individually, they often do not exhibit sufficient sensitivity and specificity on their own to merit further development as single-marker diagnostic tests. Transforming single markers into panels of markers is quite challenging. A marker with “modest credentials” may not be appealing, but such a marker may have value if it is particularly informative for a subtype of disease. Issues pertaining to assay development and intellectual property may also impede assembly of a broad set of markers for validation as a panel. 4. Discovery technologies are evolving constantly. The need to increase throughput and/or sensitivity is driving innovation. Furthermore, in-depth drilling into the proteome requires that various protein characteristics be investigated; this results in a whole slew of proteomics —omics categories that include functional proteomics to identify interesting proteins on the basis of their activity; subcellular proteomics to identify proteins in specific compartments that may be altered in disease states (i.e., the cell surface proteome, which is particularly suited for diagnostics as well as for molecular imaging and therapeutics); glycoproteomics as a study of proteins and their glycan structures that may be associated with disease; and immunoproteomics to identify immunogenic epitopes, peptidomics, and so forth. Markers that result from such proteomics —omics investigations must compete or be integrated not only with each other but also with markers discovered via genomics, transcriptomics, methylomics, and so on. Given these issues, the development of biomarkers would benefit from an organized community effort that allows progression from discovery to validation. A case in point is the National Cancer Institute’s Early Detection Research Network, which fosters a collaborative effort and provides access to critically needed standardized reference specimens as in the recent announcement of the availability of blood samples for validating lung-cancer biomarkers (http://grants.nih.gov/grants/guide/notice-files/NOTCA-07-016.html). It is time to recognize that developing biomarkers is just as complex as developing drugs and that this cannot be done on an ad hoc basis but must be done through concerted efforts that bring together representatives from academia, industry, government, and foundations.
3362 Journal of Proteome Research • Vol. 6, No. 9, 2007
SAM HANASH Fred Hutchinson Cancer Research Center
© 2007 American Chemical Society
