VEGF-121 plasma level as biomarker for response to anti-angiogenetic therapy in recurrent glioblastoma

Maurizio Martini, Ivana de Pascalis, Quintino Giorgio D'Alessandris, Vincenzo Fiorentino, Francesco Pierconti, Hany El Sayed Marei, Lucia Ricci-Vitiani, Roberto Pallini, Luigi Maria Larocca

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Abstract

Background: Vascular endothelial growth factor (VEGF) isoforms, particularly the diffusible VEGF-121, could play a major role in the response of recurrent glioblastoma (GB) to anti-angiogenetic treatment with bevacizumab. We hypothesized that circulating VEGF-121 may reduce the amount of bevacizumab available to target the heavier isoforms of VEGF, which are the most clinically relevant. Methods: We assessed the plasma level of VEGF-121 in a brain xenograft model, in human healthy controls, and in patients suffering from recurrent GB before and after bevacizumab treatment. Data were matched with patients' clinical outcome. Results: In athymic rats with U87MG brain xenografts, the level of plasma VEGF-121 relates with tumor volume and it significantly decreases after iv infusion of bevacizumab. Patients with recurrent GB show higher plasma VEGF-121 than healthy controls (p = 0.0002) and treatment with bevacizumab remarkably reduced the expression of VEGF-121 in plasma of these patients (p = 0.0002). Higher plasma level of VEGF-121 was significantly associated to worse PFS and OS (p = 0.0295 and p = 0.0246, respectively). Conclusions: Quantitative analysis of VEGF-121 isoform in the plasma of patients with recurrent GB could be a promising predictor of response to anti-angiogenetic treatment.

Original languageEnglish
Article number553
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - May 10 2018

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Keywords

  • Antiangiogenetic-therapy
  • Recurrent glioblastoma
  • Target therapy
  • VEGF isoforms

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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