Pharmacogenomic characterization of US FDA-approved cytotoxic drugs.

Peters EJ, Motsinger-Reif A, Havener TM, Everitt L, Hardison NE, Watson VG, Wagner M, Richards KL, Province MA, McLeod HL.

Source

UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Chapel Hill, Campus Box 7361, Genetic Medicine Building, Chapel Hill, NC 27599-7361, USA. hmcleod@unc.edu .

Abstract

Aims: Individualization of cancer chemotherapy based on the patient's genetic makeup holds promise for reducing side effects and improving efficacy. However, the relative contribution of genetics to drug response is unknown. Materials & methods: In this study, we investigated the cytotoxic effect of 29 commonly prescribed chemotherapeutic agents from diverse drug classes on 125 lymphoblastoid cell lines derived from 14 extended families. Results: The results of this systematic study highlight the variable role that genetics plays in response to cytotoxic drugs, ranging from a heritability of <0.15 for gemcitabine to >0.60 for epirubicin. Conclusion: Putative quantitative trait loci for cytotoxic response were identified, as well as drug class-specific signatures, which could indicate possible shared genetic mechanisms. In addition to the identification of putative quantitative trait locis, the results of this study inform the prioritization of chemotherapeutic drugs with a sizable genetic response component for future investigation. Original submitted 6 April 2011; Revision submitted 1 July 2011.