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Editing Cytoprotective Autophagy in Glioma: An Unfulfilled Potential for Therapy
Ilya Ulasov1, Jawad Fares2, Petr Timashev3
1Group of Experimental Biotherapy and Diagnostic, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow 119991, Russia.
Abstract:
Glioblastoma (GBM) resistance to the standard of care is prompting scientists to develop better targeted therapeutic strategies. Autophagy is one of the many signaling mechanisms that regulate tumor regrowth. Despite the extensive in vitro and in vivo studies published, knowledge on autophagic modulation remains scarce. This hinders the development of novel treatment modalities that employ autophagic mechanisms for the clinical benefit of patients with GBM. Clinical trials for GBM continue to fall short of showing significant survival or clinical benefit, with the complex glioma heterogeneity often being the reason to blame. Here, we propose that a combination therapy of current antiglioma regimens and autophagic mediators or suppressors can allow us to overcome GBM regrowth in the context of tumor heterogeneity.
Insights
Targeting glioblastoma (GBM) regrowth requires novel strategies. Combining standard therapies with autophagy modulators may overcome treatment resistance and tumor heterogeneity in GBM patients.
Area of Science:
- Neuro-oncology
- Cancer biology
- Cellular signaling
Background:
- Glioblastoma (GBM) exhibits resistance to standard treatments, necessitating advanced therapeutic approaches.
- Autophagy plays a critical role in regulating tumor cell regrowth and survival.
- Current understanding of autophagic modulation in GBM is limited, impeding the development of targeted therapies.
Purpose of the Study:
- To explore the potential of modulating autophagy as a therapeutic strategy for glioblastoma.
- To investigate combination therapies involving standard antiglioma regimens and autophagy modulators.
- To address the challenge of tumor heterogeneity in overcoming GBM regrowth.
Main Methods:
- Review of existing in vitro and in vivo studies on autophagy in GBM.
- Analysis of signaling pathways involved in autophagic modulation.
- Conceptual framework for combination therapy strategies.
Main Results:
- Autophagy is a key regulator of tumor regrowth in glioblastoma.
- Limited knowledge exists regarding precise autophagic modulation for therapeutic benefit.
- Tumor heterogeneity contributes to the failure of clinical trials for GBM.
Conclusions:
- Combination therapy of standard antiglioma treatments with autophagy mediators or suppressors offers a promising strategy.
- This approach has the potential to overcome glioblastoma regrowth, even within the context of tumor heterogeneity.
- Further research into autophagic modulation is crucial for advancing GBM treatment.
