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  • Review Article
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Genomic markers for decision making: what is preventing us from using markers?

Nature Reviews Clinical Oncology volume 7, pages 90–97 (2010)Cite this article

Abstract

The advent of novel genomic technologies that enable the evaluation of genomic alterations on a genome-wide scale has significantly altered the field of genomic marker research in solid tumors. Researchers have moved away from the traditional model of identifying a particular genomic alteration and evaluating the association between this finding and a clinical outcome measure to a new approach involving the identification and measurement of multiple genomic markers simultaneously within clinical studies. This in turn has presented additional challenges in considering the use of genomic markers in oncology, such as clinical study design, reproducibility and interpretation and reporting of results. This Review will explore these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the use of putative genomic markers in the clinic. Despite these rapid technological advances there is still a paucity of genomic markers in routine clinical use at present. A rational and focused approach to the evaluation and validation of genomic markers is needed, whereby analytically validated markers are investigated in clinical studies that are adequately powered and have pre-defined patient populations and study endpoints. Furthermore, novel adaptive clinical trial designs, incorporating putative genomic markers into prospective clinical trials, will enable the evaluation of these markers in a rigorous and timely fashion. Such approaches have the potential to facilitate the implementation of such markers into routine clinical practice and consequently enable the rational and tailored use of cancer therapies for individual patients.

Key Points

  • Despite extensive research, relatively few genomic markers have been implemented into routine clinical use, often because of failings in clinical study design

  • The traditional 'single disease, single genomic marker' approach does not consider tumor heterogeneity and consequently single genomic markers are often found to be inadequate biomarkers in clinical studies

  • The introduction of new high-throughput genomic technologies has enabled the simultaneous measurement of multiple genomic alterations, and has revolutionized the field of genomic marker research in oncology

  • High-throughput technologies have presented additional challenges to considering the routine clinical use of putative genomic markers

  • Putative genomic markers should undergo extensive validation before they are implemented into routine clinical practice

  • Novel adaptive clinical trial designs that incorporate genomic markers into prospective studies will enable the evaluation of markers in a rigorous, timely fashion and facilitate their implementation into clinical practice

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Figure 1: 'Marker enrichment' clinical trial design.
Figure 2: 'Planned analysis' clinical trial design.

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Authors and Affiliations

  1. Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK

    Vicky M. Coyle & Patrick G. Johnston

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  1. Vicky M. Coyle
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Correspondence to Patrick G. Johnston.

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Competing interests

Patrick G. Johnston declares he is a stock-holder for products made by Almac, Fusion Antibodies and GlaxoSmithKline. Vicky M. Coyle declares no competing interests.

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Coyle, V., Johnston, P. Genomic markers for decision making: what is preventing us from using markers?. Nat Rev Clin Oncol 7, 90–97 (2010). https://doi.org/10.1038/nrclinonc.2009.214

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