Abstract
The introduction of technologies such as mass spectrometry and protein and DNA arrays, combined with our understanding of the human genome, has enabled simultaneous examination of thousands of proteins and genes in single experiments, which has led to renewed interest in discovering novel biomarkers for cancer. The modern technologies are capable of performing parallel analyses as opposed to the serial analyses conducted with older methods, and they therefore provide opportunities to identify distinguishing patterns (signatures or portraits) for cancer diagnosis and classification as well as to predict response to therapies. Furthermore, these technologies provide the means by which new, single tumor markers could be discovered through use of reasonable hypotheses and novel analytical strategies. Despite the current optimism, a number of important limitations to the discovery of novel single tumor markers have been identified, including study design bias, and artefacts related to the collection and storage of samples. Despite the fact that new technologies and strategies often fail to identify well-established cancer biomarkers and show a bias toward the identification of high-abundance molecules, these technological advances have the capacity to revolutionize biomarker discovery. It is now necessary to focus on careful validation studies in order to identify the strategies and biomarkers that work and bring them to the clinic as early as possible.
Key Points
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Current cancer biomarkers suffer from low diagnostic sensitivity and specificity and have not yet made a major impact in reducing cancer burden
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The impressive growth of large-scale and high-throughput biology has resulted in increased popularity for the concept that novel biomarkers can be discovered through various emerging technologies
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A better understanding of the mechanisms behind biomarker elevation in biological fluids may facilitate the discovery of new tumor markers
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Some of the new promising strategies for biomarker discovery include microarray-based profiling at the DNA and mRNA level, and mass-spectrometry-based profiling at the protein or peptide level
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Study of tumor markers that include current biomarkers or examination of fluids and tissues that are in close proximity to the tumor might also assist in identification of novel tumor markers
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New tumor markers must undergo rigorous validation before they are introduced into routine clinical care
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Acknowledgements
V Kulasingam is supported by a scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC). EP Diamandis is Associate Member of the Early Detection Research Network (EDRN) and is supported by grants from the US NIH, NSERC and the Ontario Institute for Cancer Research. The authors would like to thank Carla Borgono for her assistance in generating Figure 1. CP Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.
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Kulasingam, V., Diamandis, E. Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Nat Rev Clin Oncol 5, 588–599 (2008). https://doi.org/10.1038/ncponc1187
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DOI: https://doi.org/10.1038/ncponc1187
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