The Early Detection Research Network's Specimen Reference Sets: Paving the Way for Rapid Evaluation of Potential Biomarkers
ABSTRACT BACKGROUND: The mission of the National Cancer Institute's Early Detection Research Network (EDRN) is to identify and validate cancer biomarkers for clinical use. Since its inception, EDRN investigators have learned a great deal about the process of validating biomarkers for clinical use. Translational research requires a broad spectrum of research expertise, and coordinating collaborative activities can be challenging. The EDRN has developed a robust triage and validation system that serves the roles of both "facilitator" and "brake."Content:The system consists of (a) establishing a reference set of specimens collected under PRoBE (Prospective Specimen Collection Retrospective Blinded Evaluation) design criteria; (b) using the reference set to prevalidate candidate biomarkers before committing to full-scale validation; (c) performing full-scale validation for those markers that pass prevalidation testing; and (d) ensuring that the reference set is sufficiently large in numbers and volumes of sample that it can also be used to study future candidate biomarkers. This system provides rigorous and efficient evaluation of candidate biomarkers and biomarker panels. Reference sets should also be constructed to enable high-quality biomarker-discovery research.Summary:We describe the process of establishing our system in the hope that it will serve as an example of how to validate biomarkers for clinical application. We also hope that this description of the biospecimen reference sets available from the EDRN will encourage the biomarker research community-from academia or industry-to use this resource to advance biomarkers into clinical use.
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ABSTRACT: Background: Many circulating biomarkers have been reported for the diagnosis of breast cancer, but few, if any, have undergone rigorous credentialing using prospective cohorts and blinded evaluation. Methods: The NCI Early Detection Network (EDRN) has created a prospective, multicenter collection of plasma and serum samples from 832 subjects designed to evaluate circulating biomarkers for the detection and diagnosis of breast cancer. These samples are available to investigators who wish to evaluate their biomarkers using a set of blinded samples. The breast cancer reference set is comprised of blood samples collected using a standard operating procedure at four U.S. medical centers from 2008-2010 from women undergoing either tissue diagnosis for breast cancer or routine screening mammography. The reference set contains samples from women with incident invasive cancer (n=190), carcinoma in situ (n=55), benign pathology with atypia (n=63), benign disease with no atypia (n=231), and women with no evidence of breast disease by screening mammography (BI-RADS 1 or 2, n=276). Using a subset of plasma samples (n=505) from the reference set, we analyzed 90 proteins by multiplexed immunoassays for their potential utility as diagnostic markers. Results: We found that none of these markers is useful for distinguishing cancer from benign controls. However, elevated CA-125 does appear to be a candidate marker for ER negative cancers. Conclusions: Markers that can distinguish benign breast conditions from invasive cancer have not yet been found. Impact: Availability of prospectively collected samples should improve future validation efforts. Copyright © 2014, American Association for Cancer Research.Cancer Epidemiology Biomarkers & Prevention 12/2014; 24(2). DOI:10.1158/1055-9965.EPI-14-1178 · 4.32 Impact Factor
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ABSTRACT: Cancer has been in existence longer than human beings, and man has been facing the illness ever since he made his appearance on Earth. Amazingly, the first human cancer gene was cloned only thirty years ago. This, and other extraordinary scientific goals achieved by molecular cancer research in the last 30 years, seems to suggest that definitive answers and solutions to this severe disease have been finally found. This was not the case, as cancer still remains to be defeated. To do so, cancer must be first understood. This review highlights how cancer onset and progression has been tackled from ancient times to present day. Old theories and achievements have provided the pillars of cancer understanding, in laying the basis of 'modern era' cancer research, are discussed. The review highlights the discovery of oncogenes and suppressor tumor genes, underlining the crucial role of these achievements in cancer diagnosis and therapies. Finally, an overview of how the modern technologies have given impetuous to expedite these goals is also considered.
Article: Biomarker time out[Show abstract] [Hide abstract]
ABSTRACT: The advancement of knowledge relies on scientific investigations. The timing between asking a question and data collection defines if a study is prospective or retrospective. Prospective studies look forward from a point in time, are less prone to bias and are considered superior to retrospective studies.This conceptual framework conflicts with the nature of biomarker research. New candidate biomarkers are discovered in a retrospective manner. There are neither resources nor time for prospective testing in all cases. Relevant sources for bias are not covered. Ethical questions arise through the time penalty of an overly dogmatic concept.The timing of sample collection can be separated from testing biomarkers. Therefore the moment of formulating a hypothesis may be after sample collection was completed. A conceptual framework permissive to asking research questions without the obligation to bow to the human concept of calendar time would simplify biomarker research, but will require new safeguards against bias.Multiple Sclerosis 02/2014; 20(12). DOI:10.1177/1352458514524999 · 4.86 Impact Factor