title: In vitro human cell line models to predict clinical response to anticancer drugs.
abstract: In vitro human cell line models have been widely used for cancer pharmacogenomic studies to predict clinical response, to help generate pharmacogenomic hypothesis for further testing, and to help identify novel mechanisms associated with variation in drug response. Among cell line model systems, immortalized cell lines such as Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) have been used most often to test the effect of germline genetic variation on drug efficacy and toxicity. Another model, especially in cancer research, uses cancer cell lines such as the NCI-60 panel. These models have been used mainly to determine the effect of somatic alterations on response to anticancer therapy. Even though these cell line model systems are very useful for initial screening, results from integrated analyses of multiple omics data and drug response phenotypes using cell line model systems still need to be confirmed by functional validation and mechanistic studies, as well as validation studies using clinical samples. Future models might include the use of patient-specific inducible pluripotent stem cells and the incorporation of 3D culture which could further optimize in vitro cell line models to improve their predictive validity.
authors.affiliation: Division of Clinical Pharmacology, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Nifang
authors.initials: N
authors.lastname: Niu
authors.forename: Liewei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D002461:Cell Line, Transformed / Q000187:drug effects / Q000821:virology; D045744:Cell Line, Tumor / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D060148:HapMap Project; D004854:Herpesvirus 4, Human; D006801:Humans; D066298:In Vitro Techniques; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D005819:Genetic Markers
keywords: NCI-60 panel; anticancer therapy; cancer cell line collections; drug response; in vitro human cell line models; lymphoblastoid cell lines; pharmacogenomics