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Targeting glycolysis: exploring a new frontier in glioblastoma therapy
1Department of Oncology, Suining Central Hospital, Suining, Sichuan, China.
Abstract:
Glioblastoma(GBM) is a highly malignant primary central nervous system tumor that poses a significant threat to patient survival due to its treatment resistance and rapid recurrence.Current treatment options, including maximal safe surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, have limited efficacy.In recent years, the role of glycolytic metabolic reprogramming in GBM has garnered increasing attention. This review delves into the pivotal role of glycolytic metabolic reprogramming in GBM, with a particular focus on the multifaceted roles of lactate, a key metabolic product, within the tumor microenvironment (TME). Lactate has been implicated in promoting tumor cell proliferation, invasion, and immune evasion. Additionally, this review systematically analyzes potential therapeutic strategies targeting key molecules within the glycolytic pathway, such as Glucose Transporters (GLUTs), Monocarboxylate Transporters(MCTs), Hexokinase 2 (HK2), 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), Pyruvate Kinase Isozyme Type M2 (PKM2), and the Lactate Dehydrogenase A (LDHA). These studies provide a novel perspective for GBM treatment. Despite progress made in existing research, challenges remain, including drug penetration across the blood-brain barrier, side effects, and resistance. Future research will aim to address these challenges by improving drug delivery, minimizing side effects, and exploring combination therapies with radiotherapy, chemotherapy, and immunotherapy to develop more precise and effective personalized treatment strategies for GBM.
Insights
Glioblastoma treatment is challenged by resistance and recurrence. Targeting the glycolytic pathway, particularly lactate, offers new therapeutic strategies for this aggressive brain tumor.
Area of Science:
- Neuro-oncology
- Cancer Metabolism
- Molecular Biology
Background:
- Glioblastoma (GBM) is a deadly brain cancer with poor outcomes due to treatment resistance and recurrence.
- Current therapies like surgery, radiation, and temozolomide (TMZ) have limited effectiveness.
- Glycolytic metabolic reprogramming is increasingly recognized as a key driver in GBM progression.
Purpose of the Study:
- To review the critical role of glycolytic reprogramming in GBM.
- To highlight the multifaceted functions of lactate in the GBM tumor microenvironment (TME).
- To analyze therapeutic strategies targeting key glycolytic pathway molecules.
Main Methods:
- Systematic review of literature on GBM glycolytic metabolism.
- Analysis of the role of lactate in tumor cell proliferation, invasion, and immune evasion.
- Examination of therapeutic targets including GLUTs, MCTs, HK2, PFKFB3, PKM2, and LDHA.
Main Results:
- Lactate promotes GBM cell proliferation, invasion, and immune evasion within the TME.
- Targeting glycolytic enzymes and transporters presents novel therapeutic avenues.
- Key targets include Glucose Transporters (GLUTs), Monocarboxylate Transporters (MCTs), Hexokinase 2 (HK2), PFKFB3, PKM2, and LDHA.
Conclusions:
- Targeting the glycolytic pathway, especially lactate metabolism, offers a promising strategy for GBM treatment.
- Challenges include drug delivery across the blood-brain barrier, side effects, and resistance.
- Future research should focus on combination therapies and improved drug delivery for personalized GBM treatment.
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