Key Advantages Key Disadvantages Wealth of publically available resources for LCL genotypes, which reduces the cost of genetic mapping to only the cost of the drug response phenotyping.  Difficulty of translating in vitroresults to in vivo biological/clinical relevance Fewer confounding factors compared to human clinical trials (e.g. concomitant medications, treatment regimes)  Extrapolating in vitro test concentrations to in vivo doses or exposures Amenable to robotic automation which helps maintain quality control and reduces cost of testing Cell lines amenable to immortalization may not be from the target tissue of interest for certain drugs Amenable to high-throughput testing, which allows large numbers of chemicals, concentrations, cell lines, and replicates to be tested rapidly. Not all biological pathways are represented in LCLs, which may limit its utility for certain studies Availability of genetic information allows for heritability estimation of phenotypes without needing to design complex human studies Many metabolizing enzymes (e.g. CYP450s) are not represented in LCLs and other cell lines, which  under some circumstances can make testing pro-drugs and other therapeutics challenging. LCLs can be easily manipulated to validate study findings using knock-down or forced gene expression methods.

Table 1: Key advantages and disadvantages to the LCL Model System.