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Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Glioblastoma precision therapy: From the bench to the clinic
Yuan Zhou1, Weijian Wu2, Hongye Bi3
1Department of Radiation Oncology, Tianjin Hospital, Tianjin, 300211, China; Tianjin Medical University, Tianjin, 300070, China.
Abstract:
Glioblastoma (GBM) is the most common malignancy of the central nervous system, and most patients with GBM die of the disease despite standard treatment. By clarifying the molecular abnormalities that drive the malignant phenotype of GBM, various drugs that specifically target tumor cells and the tumor microenvironment have been developed. These drugs, including drugs targeting growth factor receptors and their downstream signaling pathways, angiogenesis, aberrant metabolism, epigenetic deregulation, and aberrant immune microenvironments, have been investigated in preclinical or clinical trials. However, these drugs that significantly inhibited the growth of GBM in the preclinical stage have not produced survival benefits in patients with GBM. One reason for their failure is the lack of a definite driver gene to select patients most likely to benefit. Another reason is the inadequate pharmacokinetic properties of the drugs owing of the blood-brain barrier. In the present review, we discuss progress in the development of target therapeutic strategies. Furthermore, we discuss the development of nanomaterials that act as local drug delivery systems to penetrate the blood-brain barrier for managing GBM.
Insights
Glioblastoma (GBM) treatments struggle due to lack of targeted drugs and the blood-brain barrier. Nanomaterials offer a promising solution for effective drug delivery and improved GBM management.
Area of Science:
- Neuro-oncology
- Cancer Therapeutics
- Nanomedicine
Background:
- Glioblastoma (GBM) is a fatal central nervous system malignancy with limited treatment efficacy.
- Targeted therapies developed against GBM molecular abnormalities have shown limited clinical success.
- Challenges include identifying patient-specific drivers and overcoming the blood-brain barrier (BBB).
Purpose of the Study:
- To review advancements in targeted therapeutic strategies for Glioblastoma.
- To discuss the potential of nanomaterials as drug delivery systems for GBM management.
- To highlight strategies for overcoming BBB limitations in GBM treatment.
Main Methods:
- Review of preclinical and clinical trial data for targeted GBM therapies.
- Analysis of molecular abnormalities driving GBM.
- Exploration of nanomaterial-based drug delivery systems for CNS penetration.
Main Results:
- Targeted therapies effective in preclinical GBM models have not translated to patient survival benefits.
- Lack of specific predictive biomarkers and inadequate drug pharmacokinetics due to the BBB are key limitations.
- Nanomaterials show promise for localized drug delivery across the BBB.
Conclusions:
- Developing effective GBM treatments requires addressing molecular heterogeneity and overcoming the BBB.
- Nanomaterial-based drug delivery systems represent a promising avenue for improving GBM therapy.
- Future research should focus on targeted strategies combined with advanced delivery systems for better patient outcomes.
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