Antiangiogenic Strategies in Recurrent Glioblastoma

Recurrent glioblastoma presents a formidable therapeutic challenge owing to its highly aberrant vasculature, invasive growth and resistance to standard chemoradiation. Antiangiogenic strategies aim to disrupt the tumour’s blood supply, impede endothelial cell proliferation and normalise dysfunctional vessels. A range of approaches has been explored, including monoclonal antibodies against vascular endothelial growth factor (VEGF), inhibitors of alternative angiogenic receptors, ligand traps, and combinatorial regimens that integrate antiangiogenic agents with immunotherapy or cytotoxic drugs. Recent advances have further clarified the spatial dynamics of vascular remodelling at the tumour margin, revealed compensatory pathways that drive resistance and identified biomarkers to predict which patients may derive clinical benefit. Although inhibition of VEGF signalling frequently yields improvements in progression-free survival, overall survival gains remain elusive, underscoring the need for novel targets, optimised dosing strategies and rational combination therapies. Emerging work on endothelial cell kinase activation, targeting of endoglin and integration of innate immune effectors underscores the field’s shift towards multi-modal antiangiogenic programmes in recurrent disease.

Research from Nature Portfolio

A phase II trial investigated TRC105, a chimeric antibody directed against endoglin (CD105), in patients with glioblastoma progressing after radiotherapy, temozolomide and bevacizumab. As monotherapy, TRC105 showed limited activity, with median time to progression of approximately six weeks and upregulated plasma VEGF-A reflecting compensatory angiogenic signalling. An amended cohort received combined TRC105 and bevacizumab, achieving a median overall survival of 5.7 months and a progression-free survival of 1.8 months. The combination was well tolerated, without exacerbation of known toxicities or intracerebral haemorrhage. These findings highlight the potential of dual targeting of endoglin and VEGF pathways to overcome resistance in bevacizumab-refractory glioblastoma and support further evaluation of this combinatorial regimen.

Antiangiogenic Strategies in Recurrent Glioblastoma publication trend

The graph below shows the total number of articles in antiangiogenic strategies in recurrent glioblastoma across all publications each year (not limited to Nature Index journals).

Technical terms

Angiogenesis: The process by which new blood vessels form from pre-existing vasculature, critical for tumour growth and survival.

Vascular endothelial growth factor (VEGF): A key pro-angiogenic cytokine that stimulates endothelial cell proliferation and increases vascular permeability.

Endoglin (CD105): A membrane glycoprotein highly expressed on proliferating endothelial cells, serving as a co-receptor for transforming growth factor-β and a regulator of angiogenesis.

Tie2: A receptor tyrosine kinase on endothelial cells that, when activated, promotes vessel maturation and stability.

Progression-free survival (PFS): The interval during which a patient’s disease remains stable without radiographic or clinical evidence of progression.

Overall survival (OS): The duration from treatment initiation until death from any cause, reflecting the ultimate clinical benefit of a therapy.

References

1. An agonistic anti-Tie2 antibody suppresses the normal-to-tumor vascular transition in the glioblastoma invasion zone. Experimental & Molecular Medicine (2023).
2. Endoglin inhibitor TRC105 with or without bevacizumab for bevacizumab-refractory glioblastoma (ENDOT): a multicenter phase II trial. Communications Medicine (2023).
3. Natural killer cell therapy potentially enhances the antitumor effects of bevacizumab plus irinotecan in a glioblastoma mouse model. Frontiers in Immunology (2023).
4. Use of Bevacizumab in recurrent glioblastoma: a scoping review and evidence map. BMC Cancer (2023).