Genomic-based biomarkers of drug-induced nephrotoxicity.
Typical drug development timelines are 10 - 15 years, with high attrition rates that make it difficult for companies to sustain productive pipelines. Investigational and discovery toxicology are novel and revolutionary extensions of the field of general toxicology, which has been created to fulfil the growing need for generating higher throughput, and integrative and predictive toxicological information, in an effort to reduce attrition. Included in this new paradigm is transcript profiling, and recent innovations have led some to speculate that genomics would help revolutionise drug development, as more better predictive biomarkers of organ damage would be identified. The kidney has been a focus of toxicogenomics investigations, and candidate genomic-based biomarkers of renal damage have been identified for rodent as well as nonhuman primate models of nephrotoxicity. This review highlights published results that have led to the preliminary identification of candidate genomic-based markers of nephrotoxicity and provides insight into the future of toxicogenomics.
Davis
John W
JW
Pfizer Global Research and Development, Worldwide Safety Sciences, Chesterfield, MO 63017, USA. john.w1.davis@pfizer.com
Kramer
Jeffrey A
JA
D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D005819:Genetic Markers / Q000187:drug effects / Q000235:genetics; D023281:Genomics / Q000379:methods* / Q000639:trends; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000639:trends; D043922:Toxicogenetics / Q000379:methods* / Q000639:trends
D005819:Genetic Markers