In vitro vascular tube formation testing as a tool for treatment individualisation in patients with cervical cancer

Anticancer Res. 2011 Aug;31(8):2609-15.

Abstract

Background/aim: Targeted tumour therapies are promising, but their results in unselected patient populations are modest and tumour growth and metastasis may be promoted rather than suppressed in some cases. The present study investigates the suitability of vascular in vitro tube formation as a tool for the identification of cervical neoplasms that will respond to bevacizumab therapy.

Patients and methods: Fifteen patients with recurrent cervical cancer selected from the ongoing cervical cancer monitoring database of the Charité University Hospital Berlin, Germany, were included. Information obtained from the database included tumour stage, malignancy grade, presence of nodal metastases, lymph vessel invasion, patient age and menopausal status and serum concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin and vascular endothelial growth factor receptor 1 (VEGF-R1). Vascular tube formation was assessed with cultured human umbilical vein epithelial cells.

Results: Five patients showed a positive, 5 an inverse and 5 no in vitro response to bevacizumab. Tube length showed a marked and significant dependency on bevacizumab response. Besides tube length, VEGF-R1 concentration was the only variable with some correlation to bevacizumab response, with high levels especially for inverse responders.

Conclusion: The identification of patients with a likely benefit from targeted therapies is crucial. Tube formation shows substantial potential, but its utility needs to be confirmed in studies on the clinical rather than in vitro response to bevacizumab.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Cells, Cultured
  • Endostatins / blood
  • Endothelium, Vascular / pathology*
  • Female
  • Fibroblast Growth Factor 2 / blood
  • Humans
  • Uterine Cervical Neoplasms / blood supply
  • Uterine Cervical Neoplasms / drug therapy*
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Endostatins
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Bevacizumab