Five years ago, the National Cancer Institute’s (NCI) Division of Cancer Prevention set out to create a strong, investigator-driven network to conduct translational research to identify tests for early cancer and cancer risk. In early 2000, the Early Detection Research Network (EDRN) became a fully funded group of 28 grantees focused on the overarching goal of creating validated biomarkers ready for large-scale clinical testing. Now, in 2005, EDRN has come to fruition as a broad, interdisciplinary group with the partnerships for advancing science for public benefit and is heading into its second round of 5-year funding.
“EDRN is in the forefront of technology-driven research on the early detection of cancer and carcinogenesis,” said Sudhir Srivastava, PhD, MPH, who heads EDRN as chief of the Cancer Biomarkers Research Group in NCI. “This research will ultimately aid both detection and prevention, critical keys to eliminating cancer death, by identifying and validating biomarkers, such as proteins or genes, that can be measured to identify disease risk or progression.” The EDRN promotes collaboration among researchers by creating an environment of cross-fertilization and teamwork among different disciplines and laboratories to achieve common goals.
“A myriad of proteins and genes has been linked with a large variety of cancers and some show promise to become useful in medical practice,” said Dr. Srivastava. “However, it is prudent to validate these promising biomarkers for their intended use. There is no substitute for a validated biomarker. EDRN’s discovery, development, and delivery of cancer biomarkers will establish a strong foundation and the logistics necessary to help eliminate the suffering and death from cancer.” EDRN is a leader in the disciplined establishment and use of criteria for the validation of markers, an essential step for progress.
Critical validation studies are already in progress within EDRN. The first is a trial to determine the sensitivity and specificity of a promising molecular diagnostic technology--microsatellite analysis (MSA)-in diagnosing bladder cancer. Fifteen biomarkers in 300 patients with bladder cancer will be examined in an effort to predict recurrence of the disease. Patients with healthy bladders and those with noncancerous bladder problems that could be misdiagnosed as cancer will be used as controls. “The primary goal of this study is to monitor MSA for recurrence,” explained Dr. Srivastava, “but the longer goal is to use the test for early detection of new disease.”
The second validation study is a two-year evaluation of the use of des-gamma carboxyprothrombin (DCP) to identify individuals at risk for early-stage liver cancer. Frequent surveillance of patients with liver cirrhosis is recommended, but current procedures have shortcomings. Alpha-fetoprotein, a blood test currently used for surveillance of liver cancer, suffers from poor sensitivity and specificity. In addition, liver ultrasound is dependent on the skills and knowledge of the technician and can lead to false-negative results. This EDRN-supported study looks to improve upon these negatives.
Also underway is a three-phase study to validate a novel approach for early detection of prostate cancer based on protein expression profiling of body fluids in combination with a variety of artificial intelligence algorithms. The first phase, assessing the reproducibility and portability of the technology involved – Surface-Enhanced Laser Desorption Ionization time-of-flight mass spectrometry (SELDI-TOF-MS), a process that enables exploring and mapping proteins, is complete. Phase II, which is underway, is developing and evaluating algorithms for classifying cases and controls using these protein profiles.
EDRN is also a leader in the creative use of information technology, including sharing data through the Electronic Catalog Archiving System, and working to take complex information and display, allow its use by other researchers in intuitive ways. EDRN has pioneered the development of common data elements to speed consistency in data description across institutions and has implemented informatics solutions to enable data sharing among laboratories.
Goals of the Early Detection Research Network
- Develop and test promising biomarkers and technologies to obtain preliminary information to guide further testing
- Evaluate promising, analytically proven biomarkers or technologies, including measures of accuracy, sensitivity, specificity, and, when possible, as potential predictors of outcomes or surrogate endpoints for clinical trials
- Analyze biomarkers and their expression patterns to serve as background for large, definitive validation studies
- Collaborate with academic and industrial leaders to develop high-throughput, sensitive assay methods
- Conduct early phases of clinical and epidemiological biomarker studies
- Encourage collaboration and dissemination of information to ensure progress and avoid fragmentation
