Genomic and genetic biomarkers of toxicity.

Biomarkers in general use today are diagnostic in that they reflect an organ's ongoing dysfunction or damage. Unfortunately, in some cases the change in the biomarker occurs too late for effective medical intervention such as seen with acute renal failure. New biomarkers of toxicity are needed to (a) alert physicians of subtle changes prior to organ dysfunction or damage to enable preventive measures and (b) predict, prior to human exposure, if a drug is likely to induce toxicity in many patients or in specific individuals. Microarray technologies can move biomarker discovery forward at an unforeseen speed as tens of thousands of genes and genetic variants can be monitored simultaneously in one biological specimen. Pharmacogenomics, herein defined as the study of a drug's effect on gene expression, can be used to discover biomarkers in solid tissues or peripheral blood cells that are altered in animals or individuals following drug exposure. Pharmacogenetics, herein defined as the study of genetic factors that affect drug response, can be employed to identify individuals whose genetic make-up suggests they would respond poorly to a particular drug. Biomarkers discovered with these approaches can result in genomic/genetic tests, protein assays or other analytical tests. Examples of such are provided with a discussion of the unresolved issues that inhibit the use of toxicity biomarkers such as biomarker validation, reimbursement of clinical tests and patient privacy.