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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Cancer 1/2018

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

BMC Cancer > Ausgabe 1/2018
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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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12885-018-4442-2) contains supplementary material, which is available to authorized users.
Maurizio Martini and Ivana de Pascalis are equally contributed to the manuscript.
Roberto Pallini and Luigi Maria Larocca are shared the senior authorship.



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.


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.


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).


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.
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