Use of cell lines in the investigation of pharmacogenetic loci

Wei Zhang, M. Eileen Dolan

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations

Abstract

Drug response and toxicity, complex traits that are often highly varied among individuals, likely involve multiple genetic and non-genetic factors. Pharmacogenomic research aims to individualize therapy in an effort to maximize efficacy and minimize toxicity for each patient. Cell lines can be used as a model system for cellular pharmacologic effects, which include, but are not limited to, drug-induced cytotoxicity or apoptosis, biochemical effects and enzymatic reactions. Because severe toxicities may be associated with drugs such as chemotherapeutics, cell lines derived from healthy individuals or patients provide a convenient model to study how human genetic variation alters response to these drugs that would be unsafe or unethical to administer to human volunteers. In addition to the traditional candidate gene approaches that focus on well-understood candidate genes and pathways, the availability of extensive genotypic and phenotypic data on some cell line models has begun to allow genome-wide association (GWA) studies to simultaneously test the entire human genome for associations with drug response and toxicity. Though with some important limitations, the use of these cell lines in pharmacogenomic discovery demonstrates the promise of constructing a more comprehensive model that may ultimately integrate both genetic and non-genetic factors to predict individual response and toxicity to anticancer drugs.

Original languageEnglish (US)
Pages (from-to)3782-3795
Number of pages14
JournalCurrent Pharmaceutical Design
Volume15
Issue number32
DOIs
StatePublished - Nov 2009

Keywords

  • Drug response
  • Gene expression
  • HapMap
  • Lymphoblastoid cell lines
  • Pharmacogenomics
  • Single nucleotide polymorphism
  • Toxicity

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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