title: Recruitment of bone marrow derived cells during anti-angiogenic therapy in GBM: the potential of combination strategies.
abstract: Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which generate a network of disorganized, tortuous and permeable vessels. Recruitment of bone marrow derived cells (BMDC) is crucial for vasculogenesis. These cells may act as vascular progenitors by integrating into the newly formed blood vessels or as vascular modulators by releasing pro-angiogenic factors. In patients with recurrent GBM, anti-vascular endothelial growth factor (VEGF) therapy has been evaluated in combination with chemotherapy, yielding improvements in progression-free survival (PFS). However, benefits are temporary as vascular tumors acquire angiogenic pathways independently of VEGF. Specifically, acute hypoxia following prolonged VEGF depletion induces the recruitment of certain myeloid cell subpopulations, which highly contribute to treatment refractoriness. Here we review the molecular mechanisms of neovascularization in relation to bevacizumab therapy with special emphasis on the recruitment of BMDCs and possible combination therapies for GBM patients.
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Boer
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Annemiek M E
authors.initials: AM
authors.lastname: Walenkamp
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: w.f.a.den.dunnen@umcg.nl.
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab
keywords: Angiogenesis; Bone marrow derived cells; GBM; Resistance; VEGF