Skip Navigation

 

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 addition of protein biomarker panels to the cancer diagnostic armamentarium is an area of considerable interest in medicine. The discovery that proteins and peptides are “leaked” by tumors into clinically accessible bodily fluids such as blood and urine has led to the possibility of diagnosing cancer at an early stage or monitoring response to treatment simply by collecting these fluids and testing for the presence of cancer-related biomarkers. Prostate-specific antigen (PSA) and cancer antigen 125 (CA-125) are examples of blood-borne cancer protein biomarkers that are currently being used in the clinic. However, the measurement of individual biomarkers has clinical limitations with respect to both sensitivity and specificity. For this reason, combinations of protein/peptide analytes are under intense investigation as biomarker panels can potentially bring greater sensitivity and specificity to cancer screening than any one analyte alone. If the potential of personalized medicine is to be realized, it must include this next generation of molecular diagnostics.

We do not suffer a lack of candidate protein biomarkers: Well over 1,000 cancer protein biomarker candidates have been described in the scientific literature over the past decade, and this list continues to grow. The sobering reality, however, is that very few of these candidates have been validated, and even fewer have made it into a medical diagnostic product. This discrepancy indicates that the issue lies within the candidate biomarker pipeline.

Proteomic technologies can help make sense of the complex proteome and holds great promise for the discovery of novel cancer biomarkers. In recent years, however, studies that have applied proteomic technologies to clinical applications - such as mass spectrometry and affinity-based detection methods - have met with some disappointment.

There are two major issues at hand:

1) Variability within biomarker discovery. A complete lack of standard reagents and methods for protein identification and measurement has led to pervasive problems with reproducibility and comparison of research results between laboratories, posing a significant challenge to the translation of discoveries to clinical applications.

2) Biomarker candidates need to be pre-validated, or verified, prior to costly clinical trials. For clinical validation of protein biomarkers, an enzyme-linked immunosorbent assay (ELISA) is developed for each antigen in order to test large cohorts in clinical trials. However, these tests do not come cheap. Each ELISA takes up to one year and $2 million to develop. A more efficient biomarker development pipeline will require coupling biomarker discovery to verification in plasma prior to clinical validation. Verification is a rapid way to assess if a given candidate is detectable in blood and changes in a measurable way in relation to the presence or stage of disease. The presence of such a bridge can rapidly triage a lengthy list of candidates prior to investing very large sums of money - and time - on the development of antibodies suitable for use in an ELISA.

Traditional approaches have contributed all they can; it is time for new technologies and approaches. To make clinical cancer proteomics a reality, the scientific community must first invest in much needed technologies and infrastructure in order to build a better biomarker development pipeline. The goal of the Clinical Proteomic Technologies for Cancer (CPTC) initiative is to develop a more refined, efficient and reliable biomarker development pipeline. This pipeline is anticipated to produce better-credentialed candidate leads, ultimately accelerating the translation of new cancer biomarkers into diagnostic tests.

“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

CPTC has brought together the best minds in proteomics - an entire community devoted to fixing the pipeline - because this is far too great an endeavor for a single institution. Together, the CPTC network is laying the foundation for clinical cancer proteomics by addressing each of the following barriers:

  • Optimizing proteomic technologies and developing appropriate standards.
  • Standardizing procedures for collecting, processing, and storing biological samples used in proteomics research.
  • Making high-quality reagents available and accessible.
  • Developing technologies that can quantify proteins across a large dynamic range.
  • Developing common bioinformatics resources with shared algorithms and standards for processing, analyzing, and storing proteomic data.
  • Implementing a verification step in the protein biomarker pipeline.
  • Adopting an interdisciplinary team approach to science.

In many ways, the challenges facing the clinical proteomics community are comparable to those that were faced by the genomics community prior to the Human Genome Project (HGP) - the current technology enables the sampling of only a small portion of the proteome and at different levels of quality. Visionaries brought the HGP to life, but it was improvements made in DNA sequencing technologies that made this endeavor possible. The technologies became high-throughput, reliable, and reproducible. Had the project moved forward without these much needed technological improvements, the genomics community would never have been able to live up to its promise and the opportunities afforded by the HGP would never have been realized.

We are particularly gratified by the tremendous progress already made as we enter the third year of the program, which is a direct reflection of both the dedication to the highest quality and standards by all the CPTC members, and the deep commitment to open and collaborative science for the sake of the entire cancer proteomics community. Their work will have implications far beyond cancer proteomics, but their most lasting legacy will be the impact it will have on reducing the burden of suffering and death due to cancer. And that is the ultimate reason we are all working so hard together on ensuring 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