Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. https://doi.org/10.1056/NEJMoa043330.

Article  CAS  PubMed  Google Scholar 

Perry JR, Laperriere N, O’Callaghan CJ, Brandes AA, Menten J, Phillips C, et al. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med. 2017;376(11):1027–37. https://doi.org/10.1056/NEJMoa1611977.

Article  CAS  PubMed  Google Scholar 

Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733–40. https://doi.org/10.1200/JCO.2008.19.8721.

Article  CAS  PubMed  Google Scholar 

Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27(5):740–5. https://doi.org/10.1200/JCO.2008.16.3055.

Article  CAS  PubMed  Google Scholar 

Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med. 2017;377(20):1954–63. https://doi.org/10.1056/NEJMoa1707358.

Article  CAS  PubMed  Google Scholar 

Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709–22. https://doi.org/10.1056/NEJMoa1308345.

Article  CAS  PubMed  Google Scholar 

Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699–708. https://doi.org/10.1056/NEJMoa1308573.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bulnes S, Bengoetxea H, Ortuzar N, Argandoña E.G, Garcia-Blanco A, Rico-Barrio I, et al. Angiogenic signalling pathways altered in gliomas selection mechanisms for more aggressive neoplastic subpopulations with invasive phenotype J Signal Transduct 2012 597915 https://doi.org/10.1155/2012/597915.

Hu Q, Liu F, Yan T, Wu M, Ye M, Shi G, et al. MicroRNA-576-3p inhibits the migration and proangiogenic abilities of hypoxia-treated glioma cells through hypoxia-inducible factor-1α Int. J Mol Med. 2019;43:2387–97. https://doi.org/10.3892/ijmm.2019.4157.

Article  CAS  Google Scholar 

Liebner S, Dijkhuizen RM, Reiss Y, Plate KH, Agalliu D, Constantin G. Functional morphology of the blood-brain barrier in health and disease. Acta Neuropathol. 2018;135:311–36. https://doi.org/10.1007/s00401-018-1815-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Arvanitis CD, Ferraro GB, Jain RK. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2020;20:26–41. https://doi.org/10.1038/s41568-019-0205-x.

Article  CAS  PubMed  Google Scholar 

Mo F, Pellerino A, Soffietti R, Rudà R. Blood-brain barrier in brain tumors: biology and clinical relevance. Int J Mol Sci. 2021;22(23):12654. https://doi.org/10.3390/ijms222312654.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xiang T, Lin YX, Ma W, Zhang HJ, Chen KM, He GP, et al. Vasculogenic mimicry formation in EBV-associated epithelial malignancies. Nat Commun. 2018;9(1):5009. https://doi.org/10.1038/s41467-018-07308-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wei X, Chen Y, Jiang X, Peng M, Liu Y, Mo Y, et al. Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments. Mol Cancer. 2021;20(1):7. https://doi.org/10.1186/s12943-020-01288-1.

Article  PubMed  PubMed Central  Google Scholar 

Kim G, Ko YT. Small molecule tyrosine kinase inhibitors in glioblastoma. Arch Pharm Res. 2020;43(4):385–94. https://doi.org/10.1007/s12272-020-01232-3.

Article  CAS  PubMed  Google Scholar 

Seano G, Jain RK. Vessel co-option in glioblastoma: emerging insights and opportunities. Angiogenesis. 2020;23(1):9–16. https://doi.org/10.1007/s10456-019-09691-z.

Article  PubMed  Google Scholar 

Kuczynski EA, Reynolds AR. Vessel co-option and resistance to anti-angiogenic therapy. Angiogenesis. 2020;23(1):55–74. https://doi.org/10.1007/s10456-019-09698-6.

Article  CAS  PubMed  Google Scholar 

Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014;15:943–53.

Article  CAS  PubMed  Google Scholar 

Raizer JJ, Giglio P, Hu J, Groves M, Merrell R, Conrad C, et al. Brain tumor trials collaborative A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients. J Neurooncol. 2016;126:185–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lassen U, Sorensen M, Gaziel TB, Hasselbalch B, Poulsen HS. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Anticancer Res. 2013;33:1657–60.

CAS  PubMed  Google Scholar 

Soffietti R, Trevisan E, Bertero L, Cassoni P, Morra I, Fabrini MG, et al. Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology). J Neurooncol. 2014;116:533–41.

Article  CAS  PubMed  Google Scholar 

Gilbert MR, Pugh SL, Aldape K, Sorensen AG, Mikkelsen T, Penas-Prado M, et al. NRG oncology RTOG 0625: a randomized phase II trial of bevacizumab with either irinotecan or dose-dense temozolomide in recurrent glioblastoma. J Neurooncol. 2017;131:193–9.

Article  CAS  PubMed  Google Scholar 

Wirsching HG, Tabatabai G, Roelcke U, et al. Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial. Ann Oncol. 2018;29(6):1423–30.

Article  PubMed  Google Scholar 

Wirsching HG, Roelcke U, Weller J, et al. MRI and 18FET-PET predict survival benefit from bevacizumab plus radiotherapy in patients with IDH wild-type glioblastoma: results from the randomized ARTE trial. Clin Cancer Res. 2020;27(1):23.

Google Scholar 

Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007;11(1):83–95.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Emblem KE, Mouridsen K, Bjornerud A, Farrar CT, Jennings D, Borra RJ, et al. Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy. Nat Med. 2013;19(9):1178–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kloepper J, Riedemann L, Amoozgar Z, Seano G, Susek K, Yu V, et al. Ang2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival. Proc Natl Acad Sci U S A. 2016;113(16):4476–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Peterson TE, Kirkpatrick ND, Huang Y, Farrar CT, Marijt KA, Kloepper J, et al. Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages. Proc Natl Acad Sci U S A. 2016;113(16):4470–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hyman DM, Rizvi N, Natale R, Armstrong DK, Birrer M, Recht L, et al. Phase I study of MEDI3617, a selective angiopoietin-2 inhibitor alone and combined with carboplatin/paclitaxel, paclitaxel, or bevacizumab for advanced solid tumors. Clin Cancer Res. 2018;24(12):2749–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Groot J, Wefel JS, Cloughesy TF, Lieberman F, Chang SM, et al. Phase I trial of aflibercept (Vegf trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas. J Neurooncol. 2017;132(1):181–8.

Article  PubMed  PubMed Central  Google Scholar 

de Groot JF, Lamborn KR, Chang SM, Gilbert MR, Cloughesy TF, Aldape K, et al. Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study. J Clin Oncol. 2011;29(19):2689–95.

Article  PubMed  PubMed Central  Google Scholar 

Cher L, Nowak A, Iatropoulos G, Lee WS, Lee SY, Shim SR, et al. ACTR-75. A multicenter 3-arm open-label, phase 2a clinical trial to evaluate safety and efficacy of tanibirumab (VEGFR2 MAB) in patients with recurrent GBM assessed with K-trans and initial area under the gadolinium concentration-time curve (IUGC) Neuro Oncol. 2017;19(Suppl 6):vi17.

• Chen S, Li X, Wang H, Chen G, Zhou Y. Anti-VEGFR2 monoclonal antibody (MSB0254) inhibits angiogenesis and tumor growth by blocking the signaling pathway mediated by VEGFR2 in glioblastoma. Biochem Biophys Res Commun. 2022;604:158-164. A novel anti-VEGFR2 monoclonal antibody with promising results both in vitro and in vivo analyses.

•• Griveau A, Seano G, Shelton SJ, Kupp R, Jahangiri A, Obernier K, et al. A glial signature and Wnt7 signaling regulate glioma-vascular interactions and tumor microenvironment. Cancer Cell. 2018;33(5):874-889.e7. This study establishes vessel co-option as a mechanism of resistance to antiangiogenic agents employed by GSC.

Jung YS, Park JI. Wnt signaling in cancer: therapeutic targeting of Wnt signaling beyond β-catenin and the destruction complex. Exp Mol Med. 2020;52(2):183–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pham K, Luo D, Siemann DW, Law BK, Reynolds BA, Hothi P, et al. VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFβR signaling-dependent manner. Cancer Lett. 2015;360(1):60–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee EQ, Duda DG, Muzikansky A, Gerstner ER, Kuhn JG, Reardon DA, et al. Phase I and biomarker study of plerixafor and bevacizumab in recurrent high-grade glioma. Clin Cancer Res. 2018;24(19):4643–9.

Article  CAS