Open AccessPart 4: Pharmacogenetic Variability in Anticancer Pharmacodynamic Drug Effects
Author(s) -
Deenen Maarten J.,
Cats Annemieke,
Beijnen Jos H.,
Schellens Jan H.M.
Publication year - 2011
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2010-0261
Subject(s) - pharmacogenetics , medicine , pharmacology , pharmacodynamics , drug , drug development , pharmacogenomics , gene , genotype , genetics , biology , pharmacokinetics
Learning Objectives After completing this course, the reader will be able to: Identify genetic polymorphisms within pharmacodynamic candidate genes that are potential predictive markers for treatment outcome with anticancer drugs. Describe treatment selection considerations in patients with cancer who have genetic polymorphisms that could influence pharmacodynamic aspects of anticancer therapy.This article is available for continuing medical education credit at CME.TheOncologist.com Response to treatment with anticancer drugs is subject to wide interindividual variability. This variability is expressed not only as differences in severity and type of toxicity, but also as differences in effectiveness. Variability in the constitution of genes involved in the pharmacokinetic and pharmacodynamic pathways of anticancer drugs has been shown to possibly translate into differences in treatment outcome. The overall knowledge in the field of pharmacogenetics has tremendously increased over the last couple of years, and has thereby provided opportunities for patient‐tailored anticancer therapy. In previous parts of this series, we described pharmacogenetic variability in anticancer phase I and phase II drug metabolism and drug transport. This fourth part of a four‐part series of reviews is focused on pharmacodynamic variability and encompasses genetic variation in drug target genes such as those encoding thymidylate synthase, methylene tetrahydrofolate reductase, and ribonucleotide reductase. Furthermore, genetic variability in other pharmacodynamic candidate genes involved in response to anticancer drugs is discussed, including genes involved in DNA repair such as those encoding excision repair crosscomplementing group 1 and group 2, x‐ray crosscomplementing group 1 and group 3, and breast cancer genes 1 and 2. Finally, somatic mutations in KRAS and the gene encoding epidermal growth factor receptor ( EGFR ) and implications for EGFR‐targeted drugs are discussed. Potential implications and opportunities for patient and drug selection for genotype‐driven anticancer therapy are outlined.