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Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression.


ABSTRACT: The diversity in sarcoma phenotype and genotype make treatment of this family of diseases exceptionally challenging. Sixty-three human adult and pediatric sarcoma lines were screened with 100 FDA-approved oncology agents and 345 investigational agents. The investigational agents' library enabled comparison of several compounds targeting the same molecular entity allowing comparison of target specificity and heterogeneity of cell line response. Gene expression was derived from exon array data and microRNA expression was derived from direct digital detection assays. The compounds were screened against each cell line at nine concentrations in triplicate with an exposure time of 96 hours using Alamar blue as the endpoint. Results are presented for inhibitors of the following targets: aurora kinase, IGF-1R, MEK, BET bromodomain, and PARP1. Chemical structures, IC50 heat maps, concentration response curves, gene expression, and miR expression heat maps are presented for selected examples. In addition, two cases of exceptional responders are presented. The drug and compound response, gene expression, and microRNA expression data are publicly available at http://sarcoma.cancer.gov. These data provide a unique resource to the cancer research community.

SUBMITTER: Teicher BA 

PROVIDER: S-EPMC4636476 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression.

Teicher Beverly A BA   Polley Eric E   Kunkel Mark M   Evans David D   Silvers Thomas T   Delosh Rene R   Laudeman Julie J   Ogle Chad C   Reinhart Russell R   Selby Michael M   Connelly John J   Harris Erik E   Monks Anne A   Morris Joel J  

Molecular cancer therapeutics 20150908 11


The diversity in sarcoma phenotype and genotype make treatment of this family of diseases exceptionally challenging. Sixty-three human adult and pediatric sarcoma lines were screened with 100 FDA-approved oncology agents and 345 investigational agents. The investigational agents' library enabled comparison of several compounds targeting the same molecular entity allowing comparison of target specificity and heterogeneity of cell line response. Gene expression was derived from exon array data and  ...[more]

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