Executive Summary
“The ultimate goal of this project is to discover cancer earlier.
It’s that simple.” Leland Hartwell, Ph.D., President and Director, Fred Hutchinson Cancer Research Center; Recipient of the 2001 Nobel Prize in Physiology or Medicine
The greatest promise for early detection of cancer lies in the ability to find valid molecular indicators (or biomarkers) of the disease. Progress in cancer genetics has been rapid, but it only gives a predictive ability: We need measurements of what is happening in a patient in real time, and that means finding tell-tale protein and peptide biomarkers.
Despite a great deal of work, this has proven an extremely difficult undertaking. There are well over 1,000 cancer protein biomarker candidates that have been described in the scientific literature over the past decade, and this list continues to grow. So why is the clinical pipeline so sparse when we have all of these candidates at our fingertips? Why aren’t there a greater number of protein diagnostics already in the clinic for the early detection and treatment of cancer?
The proteomics community is struggling with this discrepancy. The NCI and experts in the field believe that part of the problem lies in technological and methodological variability, the extent of which we still do not understand entirely.
Recognizing the challenges facing the proteomics community, the NCI launched the Clinical Proteomic Technologies for Cancer (CPTC) initiative, to address and reduce the layers of variability at every step of the biomarker discovery pipeline (experimental design; sample collection and preparation; protein/peptide fractionation and detection; and protein/peptide identification and quantification – data analysis). Addressing and reducing these challenges is to be achieved through the optimization of platforms and development of appropriate standards with performance metrics, development of new technologies, development of standard operating procedures (SOPs), and development and availability of high-quality reagents for the community.
The lack of knowledge and resources explains why proteomic data are not reproducible between labs – or even within the same lab. And it explains why many of the biomarkers “discovered” turn out to be merely artifacts, failing at the clinical validation stage. This challenge is limiting the number of cancer biomarker tests that are available to the public.
Improvements in DNA sequencing launched the genomics revolution and the same will hold true for proteomics. The NCI, recognizing the promise of clinical proteomics for the early detection and treatment of cancer, has taken on this challenge.
Through the CPTC initiative, the NCI is providing critical resources to the entire cancer research community, building the foundation for the next generation of molecular diagnostics. Recognizing that launching a proteomics “revolution” will take a community, CPTC has brought together the best minds in proteomics – partnering with scientists from nearly 50 federal, academic, and private sector organizations.
This community is not only providing standards and reagents that are critically needed for optimizing proteomic technologies – they are providing a solution to advance protein biomarkers into clinically validated products faster, cheaper, and more effectively.
“CPTC will not only standardize, but improve the quality of validation criteria that’s essential to rapidly advance biomarkers into a clinical setting.”
Mark Boguski, M.D., Ph.D., Harvard Medical School, Center for BioMedical Informatics
Together, these scientists are providing a “proteomics toolkit” to the scientific community at little to no cost. These resources will provide researchers with the assurance that protein measurement results are due to changes in the biological sample and not to variability in the instrument, assay performance, reagents, operator, or site. This will dramatically improve the quality of biomarker candidates that enter the clinic.
CPTC is also improving the biomarker pipeline by implementing an extra step – verification – before clinical validation, which will serve to “pre-qualify” candidates before costly clinical trials. Like panning for gold, this extra step sifts through large biomarker candidate lists for the gold nuggets, or real biomarkers. Reproducible results across laboratories have already been generated and if this verification step can increase the number of biomarkers that get translated to clinical use, it could prove transformative to the field.
Tremendous progress has already been made and many more successes are on the horizon. The ultimate goal of the CPTC initiative is to ensure that patients reap the rewards of the molecular revolution. And that is the reason the entire community is working so hard together to ensure the success of this program.
“This program will spur the development of resources that accelerate biomarker discovery and validation, translational research, molecular diagnostics, and therapeutic monitoring. I’m convinced that when this happens, we will have built a solid foundation for proteomics in cancer.”
Henry Rodriguez, Ph.D., M.B.A., Director, CPTC
