title: Tumor-Derived Cell Lines as Molecular Models of Cancer Pharmacogenomics.
abstract: Compared with normal cells, tumor cells have undergone an array of genetic and epigenetic alterations. Often, these changes underlie cancer development, progression, and drug resistance, so the utility of model systems rests on their ability to recapitulate the genomic aberrations observed in primary tumors. Tumor-derived cell lines have long been used to study the underlying biologic processes in cancer, as well as screening platforms for discovering and evaluating the efficacy of anticancer therapeutics. Multiple -omic measurements across more than a thousand cancer cell lines have been produced following advances in high-throughput technologies and multigroup collaborative projects. These data complement the large, international cancer genomic sequencing efforts to characterize patient tumors, such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). Given the scope and scale of data that have been generated, researchers are now in a position to evaluate the similarities and differences that exist in genomic features between cell lines and patient samples. As pharmacogenomics models, cell lines offer the advantages of being easily grown, relatively inexpensive, and amenable to high-throughput testing of therapeutic agents. Data generated from cell lines can then be used to link cellular drug response to genomic features, where the ultimate goal is to build predictive signatures of patient outcome. This review highlights the recent work that has compared -omic profiles of cell lines with primary tumors, and discusses the advantages and disadvantages of cancer cell lines as pharmacogenomic models of anticancer therapies.
authors.affiliation: Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Andrew
authors.initials: A
authors.lastname: Goodspeed
authors.affiliation: Department of Biomedical Engineering, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Heiser
authors.affiliation: Department of Biomedical Engineering, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.affiliation: Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. University of Colorado Comprehensive Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado. james.costello@ucdenver.edu.
authors.forename: James C
authors.initials: JC
authors.lastname: Costello
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D018740:Genetic Heterogeneity; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents