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Updated: May 9, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Invasion as target for therapy of glioblastoma multiforme
1OncoRay - National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstraße 74, 01307 Dresden, Germany.
Abstract:
The survival of cancer patients suffering from glioblastoma multiforme is limited to just a few months even after treatment with the most advanced techniques. The indefinable borders of glioblastoma cell infiltration into the surrounding healthy tissue prevent complete surgical removal. In addition, genetic mutations, epigenetic modifications and microenvironmental heterogeneity cause resistance to radio- and chemotherapy altogether resulting in a hardly to overcome therapeutic scenario. Therefore, the development of efficient therapeutic strategies to combat these tumors requires a better knowledge of genetic and proteomic alterations as well as the infiltrative behavior of glioblastoma cells and how this can be targeted. Among many cell surface receptors, members of the integrin family are known to regulate glioblastoma cell invasion in concert with extracellular matrix degrading proteases. While preclinical and early clinical trials suggested specific integrin targeting as a promising therapeutic approach, clinical trials failed to deliver improved cure rates up to now. Little is known about glioblastoma cell motility, but switches in invasion modes and adaption to specific microenvironmental cues as a consequence of treatment may maintain tumor cell resistance to therapy. Thus, understanding the molecular basis of integrin and protease function for glioblastoma cell invasion in the context of radiochemotherapy is a pressing issue and may be beneficial for the design of efficient therapeutic approaches. This review article summarizes the latest findings on integrins and extracellular matrix in glioblastoma and adds some perspective thoughts on how this knowledge might be exploited for optimized multimodal therapy approaches.
Insights
Glioblastoma multiforme (GBM) invasion is poorly understood, hindering effective treatment. Targeting integrins and proteases may offer new therapeutic strategies for this aggressive brain cancer.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Molecular Medicine
Background:
- Glioblastoma multiforme (GBM) has a poor prognosis despite advanced treatments.
- Incomplete surgical resection due to diffuse infiltration and therapeutic resistance limit patient survival.
- Understanding GBM cell invasion mechanisms is crucial for developing effective therapies.
Purpose of the Study:
- To review current knowledge on integrins and extracellular matrix interactions in GBM.
- To explore the role of cell motility and invasion in therapeutic resistance.
- To provide perspectives on exploiting these mechanisms for multimodal therapy.
Main Methods:
- Literature review of preclinical and clinical studies on GBM invasion.
- Analysis of molecular mechanisms involving integrins and proteases.
- Discussion of therapeutic strategies targeting cell invasion.
Main Results:
- Integrins and extracellular matrix proteases regulate GBM cell invasion.
- Integrin targeting has shown promise preclinically but failed in clinical trials.
- Treatment-induced adaptations in cell motility may contribute to therapeutic resistance.
Conclusions:
- Further understanding of integrin and protease function in GBM invasion is needed.
- Targeting invasion mechanisms may enhance the efficacy of multimodal therapies.
- Exploiting knowledge of GBM cell motility and microenvironmental interactions is key for future treatment optimization.
