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Breaching barriers in glioblastoma. Part I: Molecular pathways and novel treatment approaches
Ana Miranda1, María Blanco-Prieto2, João Sousa1
1Faculty of Pharmacy, University of Coimbra, Portugal; Pharmacometrics Group of the Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, Portugal.
Abstract:
Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the most aggressive in nature. The prognosis for patients with GBM remains poor, with a median survival time of only 1-2 years. The treatment failure relies on the development of resistance by tumour cells and the difficulty of ensuring that drugs effectively cross the dual blood brain barrier/blood brain tumour barrier. The advanced molecular and genetic knowledge has allowed to identify the mechanisms responsible for temozolomide resistance, which represents the standard of care in GBM, along with surgical resection and radiotherapy. Such resistance has motivated the researchers to investigate new avenues for GBM treatment intended to improve patient survival. In this review, we provide an overview of major obstacles to effective treatment of GBM, encompassing biological barriers, cancer stem cells, DNA repair mechanisms, deregulated signalling pathways and autophagy. New insights and potential therapy approaches for GBM are also discussed, emphasizing localized chemotherapy delivered directly to the brain, immunotherapy, gene therapy and nanoparticle-mediated brain drug delivery.
Insights
Glioblastoma multiforme (GBM) treatment faces challenges due to drug resistance and the blood-brain barrier. New therapies like localized chemotherapy and nanoparticle delivery show promise for improving patient survival.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Pharmacology
Background:
- Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with poor prognosis.
- Current treatments (surgery, radiotherapy, temozolomide) are limited by drug resistance and the blood-brain barrier.
- Understanding resistance mechanisms is crucial for developing effective GBM therapies.
Purpose of the Study:
- To review the major obstacles in Glioblastoma multiforme treatment.
- To explore novel therapeutic strategies for improving patient survival.
Main Methods:
- Literature review of biological barriers, cancer stem cells, DNA repair, signaling pathways, and autophagy in GBM.
- Analysis of emerging treatment modalities including localized chemotherapy, immunotherapy, gene therapy, and nanoparticle-mediated drug delivery.
Main Results:
- Identified key challenges: biological barriers, cancer stem cells, DNA repair, signaling pathways, and autophagy.
- Highlighted potential of advanced therapies to overcome treatment resistance and improve drug delivery.
Conclusions:
- Overcoming treatment resistance and enhancing drug delivery are critical for improving Glioblastoma multiforme outcomes.
- Emerging therapies offer new hope for more effective Glioblastoma multiforme management.
