Abstract
Lymphoblastoid cell lines (LCL) are becoming popular tools for modeling drug response. LCLs, and other in vitro assays, offer the ability to test many drugs, doses, and biological samples relatively quickly and inexpensively. In addition, a unique advantage to LCLs is that they are available from a large cohort of individuals, providing the capability to test for genetic variability on a scale not readily available in other in vitro systems. Since oftentimes the genotype data is publically available, the experimental costs can be limited to the cost of the drug response phenotyping. Here we describe several advantages and limitations of LCLs. In addition we review several important aspects of LCL experimental design and statistical analysis. Lastly, we present an example of LCLs being successfully used to identify candidate single nucleotide polymorphisms and genes for variability in response to a chemotherapeutic used to treat chronic myeloid leukemia.
Highlights
In vitro models allow for the distinct advantage of interrogating molecular perturbations in human cells while controlling for a variety of experimental conditions that are otherwise not possible in human clinical trials
It is difficult to address this problem during the drug development phase due to the fact that not all populations of individuals that will end up taking the drug are adequately represented during clinical trials [1,2,3]
Epstein-Barr virus (EBV)-transformed, Lymphoblastoid cell lines (LCL), have proven useful in pharmacogenomics, especially in the realm of cancer pharmacogenomics, due to the volume of publically available genetic information on cell lines derived from large cohorts of individuals
Summary
In vitro models allow for the distinct advantage of interrogating molecular perturbations in human cells while controlling for a variety of experimental conditions that are otherwise not possible in human clinical trials. Significant heterogeneity exists in the response to many drugs, with some individuals responding well to a prescribed therapy, and other individuals with the same disorder showing minimal or no response to the same therapy. Epstein-Barr virus (EBV)-transformed, Lymphoblastoid cell lines (LCL), have proven useful in pharmacogenomics, especially in the realm of cancer pharmacogenomics, due to the volume of publically available genetic information on cell lines derived from large cohorts of individuals. This resource provides the genetic variability of a clinical trial cohort, with the study design flexibility of an in vitro study. We review advantages and disadvantages to this cell line model, and provide a brief overview of data resources, analysis techniques, and an example of a successful implementation using the LCL model
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