Pharmacogenomic characterization of US FDA-approved cytotoxic drugs.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Chapel Hill, NC 27599-7361, USA.
Eric J
EJ
Peters
Alison
A
Motsinger-Reif
Tammy M
TM
Havener
Lorraine
L
Everitt
Nicholas E
NE
Hardison
Venita G
VG
Watson
Michael
M
Wagner
Kristy L
KL
Richards
Mike A
MA
Province
Howard L
HL
McLeod
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D008040:Genetic Linkage; D006801:Humans; D010597:Pharmacogenetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents