title: Skin equivalents: a tool for the discovery and validation of pharmacodynamic biomarkers.
abstract: In the development of targeted oncology drugs, it is important to assess drug effectiveness in individual patients. We evaluated the possibility of reproducing in an ex-vivo system the biological effects observed in vitro and in vivo by the combined administration of two chemotherapeutic drugs, gemcitabine and a small inhibitor of Wee1. We found that modulation of both CDC2 phosphorylation and of a previously-identified gene signature was detectable in human skin equivalents obtained with primary keratinocytes from three individuals. Therefore, we suggest that human skin equivalents could represent a promising tool for the identification and validation of novel pharmacodynamic biomarkers.
authors: Exiris s.r.l., Rome, Italy.
authors: Chantal
authors: C
authors: Paolini
authors: Angela
authors: A
authors: Orecchia
authors: Cristina M
authors: CM
authors: Failla
authors: Paola
authors: P
authors: Gallinari
authors: Giovanna
authors: G
authors: Zambruno
authors: Christian
authors: C
authors: Steinkühler
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; D019926:Cyclin B; D009687:Nuclear Proteins; D003841:Deoxycytidine; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D000093542:Gemcitabine