title: Angiogenesis and tumor microenvironment: bevacizumab in the breast cancer model.
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.
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69373, Lyon Cedex, France, olivier.tredan@lyon.unicancer.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Trédan
authors.forename: Magali
authors.initials: M
authors.lastname: Lacroix-Triki
authors.forename: Séverine
authors.initials: S
authors.lastname: Guiu
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Mouret-Reynier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Barrière
authors.forename: François-Clément
authors.initials: FC
authors.lastname: Bidard
authors.forename: Antoine-Laurent
authors.initials: AL
authors.lastname: Braccini
authors.forename: Olivier
authors.initials: O
authors.lastname: Mir
authors.forename: Christian
authors.initials: C
authors.lastname: Villanueva
authors.forename: Philippe
authors.initials: P
authors.lastname: Barthélémy
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic; D018579:Patient Selection; D011237:Predictive Value of Tests; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab