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

M. Martini, I. de Pascalis, Q.G. D'Alessandris, V. Fiorentino, F. Pierconti, H.E.-S. Marei, L. Ricci-Vitiani, R. Pallini, L.M. 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. © 2018 The Author(s).
Original languageEnglish
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - 2018

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Keywords

  • Antiangiogenetic-therapy
  • Recurrent glioblastoma
  • Target therapy
  • VEGF isoforms
  • bevacizumab
  • tumor marker
  • vasculotropin 121
  • angiogenesis inhibitor
  • isoprotein
  • vasculotropin A
  • VEGFA protein, human
  • animal experiment
  • animal model
  • antiangiogenic therapy
  • Article
  • cancer chemotherapy
  • cancer recurrence
  • controlled study
  • glioblastoma
  • glioma
  • human
  • human cell
  • human tissue
  • male
  • molecularly targeted therapy
  • nonhuman
  • overall survival
  • progression free survival
  • protein blood level
  • protein expression
  • quantitative analysis
  • rat
  • tumor volume
  • aged
  • animal
  • blood
  • brain
  • brain tumor
  • drug screening
  • female
  • middle aged
  • mortality
  • nude rat
  • pathology
  • treatment outcome
  • tumor cell line
  • tumor recurrence
  • Aged
  • Angiogenesis Inhibitors
  • Animals
  • Bevacizumab
  • Biomarkers, Tumor
  • Brain
  • Brain Neoplasms
  • Cell Line, Tumor
  • Female
  • Glioblastoma
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Progression-Free Survival
  • Protein Isoforms
  • Rats, Nude
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Xenograft Model Antitumor Assays

Cite this

Martini, M., de Pascalis, I., D'Alessandris, Q. G., Fiorentino, V., Pierconti, F., Marei, HE-S., Ricci-Vitiani, L., Pallini, R., & Larocca, L. M. (2018). VEGF-121 plasma level as biomarker for response to anti-angiogenetic therapy in recurrent glioblastoma. BMC Cancer, 18(1). https://doi.org/10.1186/s12885-018-4442-2