title: Application of T cell-based transcriptomics to identify three candidate biomarkers for monitoring anti-TGFbetaR therapy.
abstract: OBJECTIVE
  The development of targeted drugs would greatly benefit from the simultaneous identification of biomarkers to determine the aspects of bioactivity, drug safety and efficacy, particularly when affecting receptor-signaling pathways. However, the establishment of appropriate systems to monitor drug-induced events requires an accessible surrogate tissue for functional read out.
  
  
  METHODS
  Therefore we present a universal platform based upon T cell-based gene expression profiling for the identification of biomarkers using the antitransforming growth factor beta receptor inhibitor LY2109761 as an example.
  
  
  RESULTS
  Our initial screen revealed 12 candidate genes specifically regulated in T cells by the inhibitor. In subsequent in-vitro and in-vivo analyses, the combined monitoring of independent gene regulation of three genes was established in peripheral blood mononuclear cells as novel pharmacodynamic candidate biomarkers for antitransforming growth factor beta receptor based therapies.
  
  
  CONCLUSIONS
  Overall, the proposed concept of biomarker identification can be easily adapted towards other drug candidates for whom gene regulation can be established in cellular components of peripheral blood.
authors.affiliation: Genomics and Immunoregulation, LIMES (Life and Medical Sciences Bonn), University of Bonn, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Classen
authors.forename: Christine
authors.initials: C
authors.lastname: Muth
authors.forename: Svenja
authors.initials: S
authors.lastname: Debey-Pascher
authors.forename: Daniela
authors.initials: D
authors.lastname: Eggle
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mallmann
authors.forename: Christian
authors.initials: C
authors.lastname: Rudlowski
authors.forename: Thomas
authors.initials: T
authors.lastname: Zander
authors.forename: Martin
authors.initials: M
authors.lastname: Pölcher
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.forename: Michael
authors.initials: M
authors.lastname: Lahn
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.forename: Andrea
authors.initials: A
authors.lastname: Staratschek-Jox
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D015415:Biomarkers; C530108:LY2109761; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011758:Pyrroles; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I