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A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Biomarkers for anti-vascular endothelial growth factor drugs
Sho Kuriyama1, Takeshi Yamada1, Akihisa Matsuda1
1Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8603, Japan.
Abstract:
Angiogenesis is regulated by interactions between vascular endothelial growth factors (VEGFs) and VEGF receptors. VEGF-A, VEGF-D, placental growth factor (PlGF) and plasminogen activator inhibitor-1 (PAI-1) have tumor angiogenic activity. VEGF-A and PAI-1 levels in the blood may impact the activity of bevacizumab, and VEGF-D levels may similarly diminish the efficacy of ramucirumab. However, the dynamics of these angiogenic biomarkers for anti-VEGF therapy have not been well established; therefore, they were evaluated in this retrospective study, which included two cohorts. Cohort 1 included patients who were treated with cytotoxic agents and bevacizumab as first-line chemotherapy, and Cohort 2 comprised patients who were treated with cytotoxic agents and anti-VEGF drugs (bevacizumab, ramucirumab or aflibercept) as second-line chemotherapy. VEGF-A, VEGF-D, PlGF and PAI-1 levels were measured before starting chemotherapy and were re-assessed every 1-2 months until disease progression. Bevacizumab had reduced benefit as a first-line chemotherapeutant in patients with very low or very high levels of VEGF-A. Bevacizumab increased VEGF-A and PlGF levels, but not VEGF-D or PAI-1. Anti-VEGF drugs offered the greatest benefit to patients with high PAI-1 before first- and second-line chemotherapy. PAI-1 levels were not affected by anti-VEGF drugs. Since ramucirumab increased VEGF-D, it offered less benefit to patients with high VEGF-D in second-line chemotherapy. Conversely, aflibercept offered greater benefits to patients with high VEGF-D, without increasing VEGF-D. These biomarkers may be useful for the prediction of drug efficacy and may predict resistance to anti-VEGF drugs.
Insights
Angiogenic biomarker levels, including vascular endothelial growth factor-A (VEGF-A) and plasminogen activator inhibitor-1 (PAI-1), can predict patient response to anti-VEGF therapies like bevacizumab and ramucirumab.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Angiogenesis, crucial for tumor growth, is regulated by vascular endothelial growth factors (VEGFs) and their receptors.
- Specific biomarkers like VEGF-A, VEGF-D, placental growth factor (PlGF), and plasminogen activator inhibitor-1 (PAI-1) influence anti-VEGF drug efficacy.
- The dynamic changes and predictive value of these angiogenic biomarkers in response to anti-VEGF therapy remain incompletely understood.
Purpose of the Study:
- To evaluate the dynamics of angiogenic biomarkers (VEGF-A, VEGF-D, PlGF, PAI-1) during anti-VEGF therapy.
- To determine the predictive value of these biomarkers for treatment efficacy and resistance.
- To assess the impact of baseline and changing biomarker levels on patient outcomes with bevacizumab, ramucirumab, and aflibercept.
Main Methods:
- Retrospective study analyzing two patient cohorts receiving first- and second-line chemotherapy with anti-VEGF agents.
- Measurement of VEGF-A, VEGF-D, PlGF, and PAI-1 levels at baseline and serially (every 1-2 months) until disease progression.
- Correlation of biomarker levels with treatment response and clinical outcomes.
Main Results:
- Bevacizumab efficacy was reduced in patients with very low or very high VEGF-A levels.
- Bevacizumab treatment increased VEGF-A and PlGF levels, but not VEGF-D or PAI-1.
- High baseline PAI-1 levels correlated with greater benefit from anti-VEGF drugs.
- Ramucirumab efficacy was diminished in patients with high VEGF-D, partly due to increased VEGF-D levels.
- Aflibercept showed benefit in patients with high VEGF-D without increasing its levels.
Conclusions:
- Angiogenic biomarkers VEGF-A, VEGF-D, PlGF, and PAI-1 are valuable for predicting patient response to anti-VEGF therapies.
- Biomarker dynamics can indicate potential resistance mechanisms to specific anti-VEGF drugs.
- Personalized treatment strategies incorporating these biomarkers may optimize anti-VEGF therapy outcomes.
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