MEETING NEWS ease-specific proteome studies with the collection of plasma,” he says. Specifically, even if other projects find potential biomarkers in an organ, clinicians wouldn’t want to perform biopsies every time a disease is suspected; instead, they could look for those potential biomarkers in the plasma to make a diagnosis. Having a baseline list of proteins that are present in plasma is just one step of a comprehensive plan of attack. But plasma may still be valuable for discovery. Smith says, “I think there may be things that we can’t predict from [studying tissues]. There could be some biology we don’t understand.” For example, modifications could be added to or removed from proteins after they leave a tissue and enter the circulation. If those changes are not taken into account, a candidate biomarker could be missed when a researcher shifts his or her focus from the tissue to the blood
for diagnostics. Biomarker discovery could also be accelerated by forming large collabo rative groups, says Hartwell. “We need a ‘genome’-type project to tackle this big problem of biomarker discovery,” he says. “We need data standards, reagents, databases, algorithms, fund ing, and a large-scale organized activity.” Hartwell leads the ICBC, which is a multinational effort to find biomarkers for breast, liver, nasopharyngeal, ovarian, pancreatic, and stomach cancers. He points out that the U.S. National Cancer Institute recently formed the Clinical Biomarker Program, which will also coordinate a large biomarker discovery project. Another limiting step in the biomarker pipeline is assay development, says Hartwell. “If one can discover hundreds of candidates at the tissue level or the blood level, the problem
is going to be assaying the hundreds of candidates in hundreds of samples,” he explains. Although ELISA is the standard clinical assay for lowabundance proteins, it is too expensive to implement on such a large scale. Therefore, Hartwell suggests using the method of stable isotope standards and capture by anti-peptide antibodies (known as SISCAPA) and multiplereaction-monitoring MS. Some ICBC members are investigating this method to develop multiplexed assays for several potential biomarkers. Researchers say that no one correct answer exists to the biomarker discovery problem at the moment. Different approaches and perspectives are all necessary to move the field forward. “I don’t think we’re at the point of predicting which [method] is going to be the most effective yet,” says Smith. —Katie Cottingham
GOVERNMENT AND SOCIETY
U.S. FDA: Critical projects i nclude biomarker and bioinformatics development On March 16, 2006, the U.S. Food and Drug Administration (FDA) released an initial group of research topics that could help accelerate medical product development and approval. The Critical Path Opportunities Report and List (www.fda.gov/oc/initiatives/ criticalpath/reports/opp_report.pdf ) suggests 76 research topics, including some ideas that are geared toward various aspects of biomarker and bioinformatics development. The agency prepared the Critical Path Opportunities List after receiving comments from public and private stakeholders in response to its Critical Path Report, which was released in 2004. In the report, the FDA acknowledged that the rate of medical product submissions was slowing down and suggested that a long-term agency initiative was necessary to turn the tide. As part of that initiative, the FDA developed the Critical Path Opportunities List, which provides investigators with research ideas for developing better tools to evaluate and generate medical products and therapies. The list is divided into six broad ar-
eas: animal models and tools for biomarker identification and assessment, clinical trials, bioinformatics, manu-
Ideas for the taking. After consulting with scientists, the FDA has developed a list of critical research topics.
facturing, public health, and pediatrics. Of special interest to proteomics researchers are the sections on biomarkers and bioinformatics. According to the list, criteria for determining the usefulness of a biomarker should be developed. In addition, the scientific community needs standards for the DNA microarray- and proteomicsbased identification of biomarkers.
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Other biomarker topics include assessing disease-specific biomarkers and advancing the use of imaging methods to discover biomarkers. Suggested bioinformatics research topics include the development of biomarker assessment strategies, clinical trial simulations, and device performance models. To make headway on these topics, the FDA plans to support various research projects. Some of the projects will require the formation of large-scale collaborations coordinated by the FDA. One such collaboration, called the Predictive Safety Testing Consortium, was recently announced. The consortium consists of representatives from five major pharmaceutical companies that pledge to share methods derived in-house to determine the safety of new therapies. Companies will also test each other’s methods. According to the FDA, the Critical Path Opportunities List should stimulate scientists to investigate many crucial research topics that must be addressed to accelerate the approvals of medical devices and therapies. Updates on the Critical Path Initiative and funding opportunities can be found at www. fda.gov/oc/initiatives/criticalpath. —Katie Cottingham
