Related Experiment Video
Updated: Apr 1, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Current status and future directions of anti-angiogenic therapy for gliomas
Wolfgang Wick1, Michael Platten1, Antje Wick1
1Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg and German Consortium for Translational Cancer Research, German Cancer Research Center, Heidelberg, Germany (W.W., M.P., A.W., A.H., F.W.); Department of Neuroradiology, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany (A.R., M.B.).
Abstract:
Molecular targets for the pathological vasculature are the vascular endothelial growth factor (VEGF)/VEGF receptor axis, integrins, angiopoietins, and platelet-derived growth factor receptor (PDGFR), as well as several intracellular or downstream effectors like protein kinase C beta and mammalian target of rapamycin (mTOR). Besides hypoxic damage or tumor cell starvation, preclinical models imply vessel independent tumor regression and suggest differential effects of anti-angiogenic treatments on tumorous and nontumorous precursor cells or the immune system. Despite compelling preclinical data and positive data in other cancers, the outcomes of clinical trials with anti-angiogenic agents in gliomas by and large have been disappointing and include VEGF blockage with bevacizumab, integrin inhibition with cilengitide, VEGF receptor inhibition with sunitinib or cediranib, PDGFR inhibition with imatinib or dasatinib, protein kinase C inhibition with enzastaurin, and mTOR inhibition with sirolimus, everolimus, or temsirolimus. Importantly, there is a lack of real understanding for this negative data. Anti-angiogenic therapies have stimulated the development of standardized imaging assessment and the integration of functional MRI sequences into daily practice. Here, we delineate directions in the identification of molecularly or image-based defined subgroups, anti-angiogenic cotreatment for immunotherapy, and the potential of ongoing trials or modified targets to change the game.
Insights
Anti-angiogenic therapies targeting molecular pathways like VEGF have shown disappointing results in glioma clinical trials. Further research is needed to understand these outcomes and develop effective treatments.
Area of Science:
- Oncology
- Vascular Biology
- Molecular Therapeutics
Background:
- Pathological vasculature in tumors involves targets such as VEGF, integrins, angiopoietins, and PDGFR.
- Preclinical models suggest vessel-independent tumor regression and differential effects of anti-angiogenic treatments on various cell types.
Purpose of the Study:
- To review the disappointing outcomes of clinical trials using anti-angiogenic agents in gliomas.
- To explore reasons for the lack of efficacy and identify future directions for anti-angiogenic therapies in glioma treatment.
Main Methods:
- Review of clinical trial data for anti-angiogenic agents in gliomas.
- Analysis of preclinical data and molecular targets involved in angiogenesis.
- Discussion of imaging assessment and potential modifications for future trials.
Main Results:
- Clinical trials using agents like bevacizumab, cilengitide, sunitinib, and others have largely yielded disappointing results in gliomas.
- There is a significant lack of understanding regarding the negative outcomes observed in these trials.
- Anti-angiogenic therapies have, however, advanced imaging assessment techniques in clinical practice.
Conclusions:
- Despite extensive preclinical evidence, anti-angiogenic therapies have failed to demonstrate significant efficacy in glioma clinical trials.
- Future strategies may involve identifying molecularly defined subgroups, combining anti-angiogenic therapy with immunotherapy, or exploring modified targets.
- Further research is crucial to elucidate the reasons for treatment failure and to optimize anti-angiogenic approaches for glioma patients.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:10Mechanism of Angiogenesis
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...