Use of proteomics for the discovery of early markers of drug toxicity.
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.
Collins
Ben C
BC
University College Dublin, UCD School of Biomolecular and Biomedical Science, Proteome Research Centre, UCD Conway Institute, Belfi eld, Dublin 4, Ireland. ben.collins@ucd.ie.
Clarke
Ambrose
A
Kitteringham
Neil R
NR
Gallagher
William M
WM
Pennington
Stephen R
SR
D000818:Animals; D015415:Biomarkers; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007553:Isotope Labeling; D013058:Mass Spectrometry; D040901:Proteomics / Q000379:methods*; D014116:Toxicology / Q000379:methods*
D015415:Biomarkers