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'Toxgnostics': an unmet need in cancer medicine

Nature Reviews Cancer volume 14, pages 440–445 (2014)Cite this article

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Abstract

If we were to summarize the rationale that underpins medical oncology in a Latin aphorism, it might be 'veneno ergo sum'; that is, I poison, therefore I am. The burden of chemotherapy-associated toxicity is well recognized, but we have relatively few tools that increase the precision of anticancer drug prescribing. We propose a shift in emphasis from the focussed study of polymorphisms in drug metabolic pathways in small sets of patients to broader agnostic analyses to systematically correlate germline genetic variants with adverse events in large, well-defined cancer populations. Thus, we propose the new science of 'toxgnostics' (that is, the systematic, agnostic study of genetic predictors of toxicity from anticancer therapy).

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Figure 1: Proposed clinical trial paradigm for the discovery of 'toxgnostics' markers though genome-wide association studies (GWAS).

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Acknowledgements

Core funding to the Wellcome Trust Centre for Human Genetics was provided by the Wellcome Trust (090532/Z/09/Z).

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Authors and Affiliations

  1. Department of Oncology, Oxford Cancer Centre, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK

    David Church & Rachel Kerr

  2. Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    David Church

  3. Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Enric Domingo, Dan Rosmarin, Claire Palles & Ian Tomlinson

  4. Genomic Medicine Theme, Oxford Comprehensive Biomedical Research Centre, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Ian Tomlinson

  5. Oxford Cancer Biomarkers, The Magdalen Centre, Oxford Science Park, Robert Robinson Avenue, Oxford, OX4 4GA, UK

    Kevin Maskell

  6. Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK

    David Kerr

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Correspondence to David Kerr.

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D.K. is a co-founder of and owns stock in Oxford Cancer Biomarkers, Oxford, UK. R.K. owns stock in Oxford Cancer Biomarkers. K.M. is an employee at Oxford Cancer Biomarkers. I.T. is a consultant for Oxford Cancer Biomarkers. All other authors declare no competing interests.

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Church, D., Kerr, R., Domingo, E. et al. 'Toxgnostics': an unmet need in cancer medicine. Nat Rev Cancer 14, 440–445 (2014). https://doi.org/10.1038/nrc3729

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