Drug resistance mechanisms and novel therapeutic strategies for anti-vegf therapy in patients with glioblastoma

Farzan Mozaffarian,1,* Mohammad amin dehghani,2 Mahsa kaviani,3 Fatemeh dehghani ,4

1. School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2. Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3. School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4. Department of Genetics, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Introduction

Anti-vegf-a therapy is one of the standard postoperative treatments for recurrent glioblastoma (gbm). however, the temporary benefical effects of this strategy are unable to improve the overall survival of the patient. among which, bevacizumab as a humanized monoclonal anti-vegf-a antibody exhibited positively potent activities against gbm, including lowering tumor growth and prolonging progression-free survival (pfs). bevacizumab-resistance glioblastoma cells producing vegfr2 undermined autocrine vegf-c/vegfr2 signaling in glioblastoma.

Methods

The search procedure in english regarding the study subject was fulfilled on pubmed database using the keywords of gbm; vegf; anti-vegf; bevacizumab; drug resistance and gbm treatment.

Results

The histological features of gbms showed a high rate of vascular proliferation mediated by vegf, highlighting the necessity of finding novel targeted anti-angiogenic therapies, such as the monoclonal anti-vegf-a antibody bevacizumab, to reduce tumor angiogenesis, especially in several phase ii trials. the sustained vegfr2 activation and tumor growth may occur by vegf-c, whose inhibition can effectively control the tumor in comparison with the treatment with bevacizumab. however, the applied problem of antiangiogenic drugs in treating the cancer is the drug resistance, which mainly can be reportedly attributed to intrinsic non-responsiveness and adaptive resistance in which the resistance emerges following the initial tumour responds because of being upregulation of other angiogenic routes.

Conclusion

The vascularization is decreased along with the gsc population because the anti-vegf-a anti-angiogenic antibody bevacizumab targets the gbm perivascular niche. however, there are controversy reports on the effectiveness of anti-vegf approaches to treat the gbm, suggesting further research to seek alternative pro-angiogenic pathways, mechanisms of resistance, combination strategies, and biomarkers to predict therapeutic response.

Keywords

Gbm; anti-vegf; bevacizumab; drug resistance; gbm treatment.