Sarcoma cell line screen of oncology drugs and investigational agents identifies patterns associated with gene and microRNA expression

Beverly A. Teicher, Eric Polley, Mark Kunkel, David Evans, Thomas Silvers, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, Michael Selby, John Connelly, Erik Harris, Anne Monks, Joel Morris

Research output: Contribution to journalArticle

15 Citations (Scopus)

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, andmiR 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.

Original languageEnglish (US)
Pages (from-to)2452-2462
Number of pages11
JournalMolecular Cancer Therapeutics
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

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Investigational Drugs
MicroRNAs
Sarcoma
Gene Expression
Cell Line
Hot Temperature
Aurora Kinases
Mitogen-Activated Protein Kinase Kinases
Inhibitory Concentration 50
Libraries
Exons
Neoplasms
Genotype
Pediatrics
Phenotype
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sarcoma cell line screen of oncology drugs and investigational agents identifies patterns associated with gene and microRNA expression. / Teicher, Beverly A.; Polley, Eric; Kunkel, Mark; Evans, David; Silvers, Thomas; Delosh, Rene; Laudeman, Julie; Ogle, Chad; Reinhart, Russell; Selby, Michael; Connelly, John; Harris, Erik; Monks, Anne; Morris, Joel.

In: Molecular Cancer Therapeutics, Vol. 14, No. 11, 01.11.2015, p. 2452-2462.

Research output: Contribution to journalArticle

Teicher, BA, Polley, E, Kunkel, M, Evans, D, Silvers, T, Delosh, R, Laudeman, J, Ogle, C, Reinhart, R, Selby, M, Connelly, J, Harris, E, Monks, A & Morris, J 2015, 'Sarcoma cell line screen of oncology drugs and investigational agents identifies patterns associated with gene and microRNA expression', Molecular Cancer Therapeutics, vol. 14, no. 11, pp. 2452-2462. https://doi.org/10.1158/1535-7163.MCT-15-0074
Teicher, Beverly A. ; Polley, Eric ; Kunkel, Mark ; Evans, David ; Silvers, Thomas ; Delosh, Rene ; Laudeman, Julie ; Ogle, Chad ; Reinhart, Russell ; Selby, Michael ; Connelly, John ; Harris, Erik ; Monks, Anne ; Morris, Joel. / Sarcoma cell line screen of oncology drugs and investigational agents identifies patterns associated with gene and microRNA expression. In: Molecular Cancer Therapeutics. 2015 ; Vol. 14, No. 11. pp. 2452-2462.
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