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Updated: Apr 24, 2026
Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
Angiogenesis and tumor microenvironment: bevacizumab in the breast cancer model
Olivier Trédan1, Magali Lacroix-Triki, Séverine Guiu
1Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69373, Lyon Cedex, France, olivier.tredan@lyon.unicancer.fr.
Abstract:
Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. Antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. According to Jain et al., an alternative hypothesis could be that certain antiangiogenic agents can also transiently "normalize" the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. With emphasize on the research works of Jain et al., the aim of this review is to describe the impact of antivascular endothelial growth factor (VEGF) therapy on "pseudo-normalization" of tumor vasculature and tumor microenvironment, its role in early and metastatic breast cancer, and the clinical evidence supporting this original concept. The phase III clinical trials showed that extended tumors, metastatic or locally advanced, are likely to benefit from bevacizumab therapy in combination with chemotherapy, assuming that a high level of tumor neoangiogenesis as in triple-negative tumors is the best target. In adjuvant setting, the lower level of tumor vasculature could mask a potential benefit of anti-VEGF therapy. All these findings highlight the need to identify biomarkers to help in the selection of patients most likely to respond to anti-VEGF therapy, to better understand the mechanism of angiogenesis and of resistance to anti-VEGF therapy according to molecular subtypes.
Insights
Anti-VEGF therapy may normalize tumor vasculature, improving oxygen and drug delivery. Research highlights its potential in breast cancer, emphasizing biomarker identification for patient selection.
Area of Science:
- Oncology
- Vascular Biology
- Cancer Therapy
Background:
- Solid tumors depend on blood vessels for growth, leading to antiangiogenic therapies targeting tumor vasculature.
- Antiangiogenic agents, like those targeting vascular endothelial growth factor (VEGF), may also "normalize" tumor vasculature, enhancing drug and oxygen delivery.
Purpose of the Study:
- To review the impact of anti-VEGF therapy on tumor vasculature "pseudo-normalization" and the tumor microenvironment.
- To explore the role of anti-VEGF therapy in early and metastatic breast cancer.
- To examine clinical evidence supporting the concept of tumor vasculature normalization.
Main Methods:
- Review of research works by Jain et al. focusing on anti-VEGF therapy.
- Analysis of phase III clinical trials involving bevacizumab in combination with chemotherapy.
- Examination of tumor neoangiogenesis and vasculature levels in different breast cancer settings.
Main Results:
- Phase III trials suggest bevacizumab therapy benefits advanced or metastatic breast cancer, particularly triple-negative tumors with high neoangiogenesis.
- In the adjuvant setting, lower tumor vasculature may obscure the benefits of anti-VEGF therapy.
- Tumor vasculature "pseudo-normalization" by anti-VEGF agents impacts the tumor microenvironment.
Conclusions:
- Identifying biomarkers is crucial for selecting patients who will respond to anti-VEGF therapy.
- Further understanding of angiogenesis and resistance mechanisms is needed, especially concerning molecular subtypes.
- Anti-VEGF therapy's role in breast cancer treatment warrants continued investigation, considering vasculature normalization.
