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NCI Approves New $104 Million Initiative To Optimize, Enhance Proteomic Tools

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Aiming to optimize current proteomic technologies, make proteomic reagents more available, and develop new proteomic technologies, the National Cancer Institute's Board of Scientific Advisors has approved a $104 million budget for a new program called the Clinical Proteomics Technologies Initiative.

The NCI plans to issue requests for applications and requests for proposals for the new program in the fall, according to Gregory Downing, the director of the NCI's Office of Technology and Industrial Relations. Funding for projects will be given out over five years.

Though the fidelity of proteomic instruments, namely mass spectrometers, is generally believed to be quite good, the proteomics field has been somewhat frustrated by its current ability to identify unique features of cancer at the protein level that can be used for early disease detection, Downing said.

For example, in the quest for ovarian cancer biomarkers, a large-scale study found an inflammatory mediator, transthyretin, as one of the markers for the disease. Inflammatory mediators are not very sensitive or specific for cancer diseases, Downing pointed out.

Furthermore, there was no correlation in biomarkers between two published ovarian cancer studies — one study reported three biomarkers for the disease, while another study reported four completely different biomarkers for the disease.

"[The lack of correlation] has been pretty frustrating for our community," Downing told ProteoMonitor this week. "This new initiative is really about enhancing the capabilities for characterizing specimens from patients, identifying features in them and quantifying [the features]."

The first part of the Clinical Proteomics Technologies Initiative is geared towards setting up clinical proteomics technology-assessment consortia, composed of cancer biologists, statisticians, epidemiologists, and technologists. The consortia will evaluate proteomic tools, such as mass specs and proteins arrays, and develop protocols to improve standardization of proteomics experiments.


The lack of correlation between biomarkers for the same disease "has been pretty frustrating for our community. This new initiative is really about enhancing the capabilities for characterizing specimens from patients, identifying features in them and quantifying [the features]."

In addition, the consortia will perform cross-laboratory studies of common sample sets to evaluate data reproducibility and provide consulting services and training to the proteomics community.

The budget for the assessment consortia is $8.5 million for the first year, and $35.5 million total over five years. Five awards are expected to be given out for this part of the initiative.

The second part of the initiative aims to develop innovative tools, including data-processing algorithms, for enabling protein and peptide measurement. This part of the initiative has been given a budget of $8 million for the first year and $56 million over five years. Ten awards are expected to be given out for this part of the initiative.

"Scientists are generating huge data sets and they don't have strong enough analytical tools for processing the data," Downing said. "Help with [data processing] algorithms is necessary."

The third part of the initiative aims to develop a clinical proteomics reagents resource. This part of the initiative stems from a series of workshops with both industry and academic scientists during which some researchers told NCI officials that they lacked access to high-quality antibodies, proteins, and peptides that were well characterized and affordable.

The NCI's proteomic reagents resource will characterize and produce antibodies, proteins, and peptides of interest, and make them accessible to scientists for a nominal shipping fee.

"We're not talking $200. We're talking $25 or $50," Downing said.

A similar public resource has been developed with genomics and aptamers, Downing noted. The NCI plans to issue contracts to chosen laboratories to identify and characterize epitopes, proteins, and peptides, and to produce the ones of interest. It plans to spend $2.5 million the first year and $12.5 million over five years to develop this resource. Two awards will be given out for this part of the initiative.

Coordination and management of the new Clinical Proteomics Technologies Initiative will be through a council that represents members of the assessment consortia and NCI program managers. The council will establish priorities and assess milestone achievements, and it will evaluate protocol design and analytical methods. It will report to the NCI's National Cancer Advisory Board and Board of Scientific Advisors.

Before initiating the new Clinical Proteomics Technologies Initiative, the NCI made its first foray into enhancing protein measurement technologies about a year ago with a mouse model initiative. That initiative, led by Martin Macintosh and Amanda Paulovich from the Fred Hutchinson Cancer Research Center and Samuel Hanash from the University of Michigan, aimed to develop standard protocols and mass spectrometry technologies for identifying proteins in plasma that are unique to cancer. Inter-laboratory and inter-platform assessment was done using 17 mouse models of human cancer.

The new Clinical Proteomics Technologies Initiative is another step forward in advancing the field of proteomics to become more standardized, reproducible, and higher throughput.

Anna Barker, NCI's deputy director for advanced technologies and strategic partnerships, said the new initiative builds upon a two-year process during which the NCI's Board of Scientific Advisors sought feedback from the research community through workshops and meetings about how to advance the field of cancer research.

"We heard over and over again from across the cancer research enterprise that we need to provide the community with specific support to advance the field of proteomics," Barker said.

The new initiative is not "all encompassing," Barker added, but it is a step forward that will hopefully bring the field "to a point where we can move ahead… very quickly."

— Tien-Shun Lee ([email protected])

 

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