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CPTC held its fourth annual meeting in Bethesda, MD, on September 8-9, 2010, bringing together a record number of attendees-more than 300 participants-representing the full breadth of scientific fields that contribute to the initiative's mission.

Henry Rodriguez, Ph.D., MBA, director, Office of Cancer Clinical Proteomics Research, kicked off the annual meeting by reminding attendees that the purpose of CPTC (Phase I) is to address the analytical barriers in clinical proteomic technologies. Specifically, the initiative was charged to address: (a) a lack of technology measurement reproducibility and transferability across labs; (b) a lack of technology optimization and/or development; and (c) a lack of publicly available high-quality reagents and data sets to the cancer research community. In the four years since the program's launch, CPTC has made great strides in overcoming these barriers including, but not limited to, developing an accurate and quantitative biomarker assay workflow for proteomics, incorporating technology standards, standard operating procedures (SOPs), analytical reference data sets, critically needed reagents (e.g., monoclonal antibodies) and an open access proteomics database. These new workflows address the variability of methods and technologies that exist run to run, instrument to instrument, and lab to lab; enabling scientists to accurately identify and quantify large numbers of proteins in patient samples. CPTC has also led international efforts to advance open data access policies in proteomics, called the Amsterdam Principles.

Opening Address Sets the Stage for New CPTC Goals in Phase II

CPTC is now ready to leverage the advances made in the first phase of the program, and NCI has announced that it will fund a second phase of the initiative, providing $75 million to $120 million over the next five-year period. CPTC Phase II will establish a team of six to eight Proteome Characterization Centers (PCCs) to systematically define the functional cancer proteome that derives from defined alterations in cancer genomes in order to discover and verify protein cancer biomarker candidates. Specifically, these PCCs will use data and selected biospecimens from cancer genomics programs (e.g., The Cancer Genome Atlas to identify changes at the protein level that may reflect changes in cancer genomes. Read more in this issue of eProtein.

Paula Kim, founder of Translating Research Across Communities (TRAC) who became an advocate after her father passed away from pancreatic cancer 12 years ago, conveyed her reaction to the issue of international standards in science. "The lack of standards in science [biospecimens, proteomics, etc.] appalls me. I was totally surprised at the lack of worldwide standards. Architects, engineers-they use worldwide standards. Why not scientists?" asked Kim. She acknowledged the field had put the cart before the horse prior to this initiative, and applauded the CPTC community for their efforts in developing the standards needed in proteomics. "We must get this right. It's your responsibility to use these patient biospecimens wisely. They are counting on you. We must harness the scientific, industrial, and social will to accelerate discoveries into clinically meaningful information. Patients, families, friends, and loved ones are counting on us...because in the end it's not about you, or me, or the science-it's about the patient."

Meeting Highlights Continued Innovation within the Genomic and Proteomic Communities

The two-day meeting included a number of talks, posters, and software demonstrations featuring research being conducted by the highly collaborative, multi-disciplinary CPTC community. Research highlights included protein biomarker discovery technology platforms, the role of post-translational modifications in cancer, bioinformatics resources and tools, quantitative proteomics, reagents development, and clinical applications.

Both days featured a number of keynote addresses by prominent scientists speaking on a diverse range of topics. Forest M. White, Ph.D., assistant professor, Department of Biological Engineering, Massachusetts Institute of Technology, spoke on the challenge of getting from known genetic mutation to a cancer therapeutic. "Mutation re-wires the signaling network. If we can identify the re-wiring, we can identify the best treatment options. Think of it [the signaling network] like a circuit board: How is the signal being sent around the mutation? Target that and you crash the system," said White. He and his colleagues are trying to understand how mutations within the phosphorylation domains of the epidermal growth factor receptor (EGFR) re-wire the signaling network in glioblastoma multiforme and how these biological insights can be translated into therapeutic strategies.

Paul Spellman, staff scientist, Lawrence Berkeley National Laboratory, Berkeley, California, discussed recent findings from The Cancer Genome Atlas (TCGA) regarding The Ovarian Cancer Genome. His talked focused on how these findings can be translated and integrated into proteomic expeditions/survey analysis to develop a more complete understanding of the molecular and phenotypic hallmarks of ovarian cancer.

Lynda Chin, M.D., professor of dermatology, Harvard Medical School and Dana-Farber Cancer Institute, began by stating that cancer is a disease of the genome and that what we don't know can, in fact, hurt us. This "not knowing" was the motivation behind TCGA, of which Chin is actively involved as both a Principal Investigator and member of the Executive Subcommittee. "Understanding the impact of genomic changes in the proteome is critically important," said Chin, who is using mouse models of human cancers to assess the function of genomic alterations and distinguish the drivers from the passengers. Specifically, Chin and colleagues are using cancer genomics to facilitate the discovery of prognostic biomarkers by searching for genomic alterations that can identify metastatic risk.

Speakers Call for Bold Vision, Setting Higher Bar to Advance Molecular-Based Medicine

Anna Barker, Ph.D., former deputy director, NCI, began her presentation by commenting that the CPTC initiative is one of NCI's best. "This program has taken us all the way to [biomarker] verification. I give those in this room a lot of credit because it's not sexy, but what they have accomplished is quite profound," said Barker. She then stated that cancer biomarkers are going to be proteins and/or protein signatures, and that a big and bold vision is needed if proteomics is going to lay the foundation for molecular-based medicine. This vision includes supporting the full implementation of caHUB for quality biospecimens, partnering with nanotechnology, organizing around functional aspects of cancer, practicing team-based science, and including the private sector to tie these efforts into diagnostic tests because government cannot do this on its own. "Somebody needs to jump-start the field of molecular diagnostics," said Barker, who also expressed concern that these advances will develop offshore in other countries if action is not taken. "I have seen this [happen] with other fields, and I can see it happening in this field as well."

Joshua LaBaer, M.D., Ph.D., director, Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, followed Dr. Barker by stating that academia needs to take a leading role in biomarker research because, "there is not enough upside for industry to invest in discovery. Industry is willing to take biomarkers only after they have been validated." LaBaer also commented on the challenges of finding validated, clinically useful biomarkers, which include, "biology, biology, biology-journals don't publish negative results [resulting in duplicative efforts], validation is not sexy, and scientists cannot get grants to do validation studies." LaBaer believes that a higher bar is needed for biomarker discovery publications, to include preliminary validation, and a mechanism is also needed for disseminating negative results because killing a bad biomarker is important.

CPTC has made tremendous progress-including development of a new protein biomarker pipeline, regulatory science, open data access policies, and renewable affinity reagents-which is indicative of its investigators' dedication to the highest quality of research. CPTC is a testament that team-based science can be very successful, and its progress to date has laid the groundwork for future success in systematically linking genomics to proteomics to aid in the identification of evidence-based targets that can drive the development of new diagnostics and therapeutics for cancer.