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The human body produces about a million different proteins. Because they are involved in every aspect of cell function and dysfunction, identifying differences in proteins between the normal and cancerous states should provide new insights into how cancer develops and progresses and could lead to new methods of diagnosis, treatment, and prevention. Therefore, proteomics, or the comprehensive study of the full complement of proteins produced by a cell or organism—as well as any changes that occur over time or under varying conditions—is an area of intense research.
In 2006, NCI launched the Clinical Proteomic Technologies for Cancer (CPTC) initiative to address issues impeding the advance of proteomics research, including 1) the variability in experimental designs; 2) the variability in technological and technical aspects of protein identification; 3) the variability in biospecimen collection; 4) the variability in data acquisition, analysis, and reporting; 5) a lack of reproducible proteomic technologies; and 6) a lack of highly characterized and standardized reagents. This initiative, which ended in 2011, included three integrated programs that worked together to overcome these issues:
- Clinical Proteomic Technology Assessment for Cancer network: A network of five multidisciplinary teams that collaborated on research projects to identify and understand the experimental and analytical sources of error with existing technologies
- Advanced Proteomic Platforms and Computational Sciences program: Individual investigators who developed new analytical tools, technology, and software to improve the accuracy and reproducibility of proteomic measurements
- Proteomic Reagents and Resources program: This program provided high-quality, well-characterized reagents (antibodies), data, and standard reference materials for the research community
The institutions selected to participate in the CPTC were chosen, in part, for the broad expertise of their proteomic research teams. These institutions included Memorial Sloan-Kettering Cancer Center, Purdue University, the University of California San Francisco/Lawrence Berkeley National Laboratory/Buck Institute, Vanderbilt University School of Medicine (which includes the Vanderbilt-Ingram Cancer Center), and the Broad Institute of MIT and Harvard, in conjunction with the Fred Hutchinson Cancer Research Center.
In one CPTC study, reported in Nature Biotechnology in 2009, a team of researchers led by Dr. Steven A. Carr of the Broad Institute showed that the results of proteomic assays using a technique called multiple reaction monitoring coupled with stable isotope dilution mass spectrometry, or MRM-SID-MS, can be highly reproducible from laboratory to laboratory and with different instrument platforms when common materials and standardized protocols are used. In the published report, Carr and his colleagues also provided data and benchmarks against which individual laboratories can compare their performance in studying and quantifying proteins in blood.
Finding Protein Biomarkers for Cancer
In 2011, NCI launched the Clinical Proteomic Tumor Analysis Consortium (CPTAC) to characterize the proteomic content of tumors analyzed in The Cancer Genome Atlas (TCGA) project. The CPTAC will systematically identify proteins and related biological processes that are affected by the alterations that occur in cancer genomes. Findings from the CPTAC should further our understanding of cancer biology at the protein level and, hopefully, will improve our ability to diagnose, treat, and prevent cancer.
The CPTAC includes eight Proteome Characterization Centers (PCCs). Five of these PCCs are based at NCI-designated cancer centers, including the Siteman Cancer Center at Washington University in St. Louis, the UNC Lineberger Comprehensive Cancer Center, the Sidney Kimmel Cancer Center at Johns Hopkins University, the Fred Hutchinson Cancer Research Center, and the Vanderbilt-Ingram Cancer Center.