Use of proteomics for the discovery of early markers of drug toxicity

Abstract

Toxicity and safety issues remain a significant problem for drug development efforts by pharmaceutical and biotechnology companies. Exisiting early biomarkers of toxicity are insufficient and this is demonstrated by the high failure rate of candidate therapeutics due to toxicity problems. It is anticipated that the advent of ‘omic’ technologies should facilitate a comprehensive understanding of the perturbation of biological systems by toxic insults and, as such, will lead to better predictive models of toxicity for use in drug development. The field of proteomics continues to develop rapidly and it is already evident that proteomic approaches have much to contribute to the field of ‘systems toxicology’ and to the development of novel biomarkers of toxicity. Here, the key proteomic approaches are reviewed, their applications in pharmaceutical toxicology are described and what shape future developments in this arena might take is considered.

Keywords::

• pharmaceutical toxicology
• predictive toxicology
• proteomics
• systems toxicology
• toxicoproteomics

Acknowledgements

Funding is acknowledged under the EU FP6 Integrated Project, InnoMed. The UCD Conway Institute and the Proteome Research Centre is funded by the Programme for Third Level Institutions (PRTLI), as administered by the Higher Education Authority (HEA) of Ireland. Funding is acknowledged from the Wellcome Trust and the Medical Research Council for work carried out at the University of Liverpool. Colleagues at Applied Biosystems, particulary T Hunt and C Hunter, are thanked for their invaluable contributions to toxicology projects undertaken in the University of Liverpool and University College Dublin. R Jenkins is thanked for many helpful discussions.

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