Pharmacogenomic biomarkers: validation needed for both the molecular genetic mechanism and clinical effect

Abstract

Drug therapy can be ineffective or cause adverse reactions in a subset of patients. Pharmacogenomic biomarkers afford the opportunity to optimize an individual’s therapy. Yet, few tests are currently part of standard care. To validate biomarkers, clinical replication studies are essential. Equally important, but less appreciated, the genetic mechanisms must also be understood to facilitate translation into clinical use. Representing main contributors to genetic variability, regulatory polymorphisms in particular are still poorly studied (e.g., 5-HTTLPR). This article focuses on molecular and functional diversity of genetic biomarkers, as a guide to optimal use in personalized medicine.