Skin equivalents: a tool for the discovery and validation of pharmacodynamic biomarkers

Cancer Invest. 2013 Jan;31(1):60-6. doi: 10.3109/07357907.2012.749269.

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.

MeSH terms

  • 3T3 Cells
  • Animals
  • Biomarkers / metabolism*
  • CDC2 Protein Kinase
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / metabolism
  • Cells, Cultured
  • Cyclin B / metabolism
  • Cyclin-Dependent Kinases
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Drug Screening Assays, Antitumor / methods*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Mice
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / metabolism
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Skin / drug effects*
  • Skin / metabolism*

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • Cyclin B
  • Nuclear Proteins
  • Deoxycytidine
  • gemcitabine
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases