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 language | English |
|---|---|
| Article number | 553 |
| Journal | BMC Cancer |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - May 10 2018 |
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Keywords
- Antiangiogenetic-therapy
- Recurrent glioblastoma
- Target therapy
- VEGF isoforms
ASJC Scopus subject areas
- Oncology
- Genetics
- Cancer Research
Cite this
VEGF-121 plasma level as biomarker for response to anti-angiogenetic therapy in recurrent glioblastoma. / Martini, Maurizio; de Pascalis, Ivana; D'Alessandris, Quintino Giorgio; Fiorentino, Vincenzo; Pierconti, Francesco; Marei, Hany El Sayed; Ricci-Vitiani, Lucia; Pallini, Roberto; Larocca, Luigi Maria.
In: BMC Cancer, Vol. 18, No. 1, 553, 10.05.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - VEGF-121 plasma level as biomarker for response to anti-angiogenetic therapy in recurrent glioblastoma
AU - Martini, Maurizio
AU - de Pascalis, Ivana
AU - D'Alessandris, Quintino Giorgio
AU - Fiorentino, Vincenzo
AU - Pierconti, Francesco
AU - Marei, Hany El Sayed
AU - Ricci-Vitiani, Lucia
AU - Pallini, Roberto
AU - Larocca, Luigi Maria
PY - 2018/5/10
Y1 - 2018/5/10
N2 - 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.
AB - 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.
KW - Antiangiogenetic-therapy
KW - Recurrent glioblastoma
KW - Target therapy
KW - VEGF isoforms
UR - http://www.scopus.com/inward/record.url?scp=85046630127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046630127&partnerID=8YFLogxK
U2 - 10.1186/s12885-018-4442-2
DO - 10.1186/s12885-018-4442-2
M3 - Article
C2 - 29747600
AN - SCOPUS:85046630127
VL - 18
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 553
ER -