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Updated: Aug 1, 2025
Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
Expert opinion on translational research for advanced glioblastoma treatment
Xiaoteng Cui1, Yunfei Wang1, Junhu Zhou1
1Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin 300052, China.
Abstract:
Malignant gliomas are known to be one of the most difficult diseases to diagnose and treat because of the infiltrative growth pattern, rapid progression, and poor prognosis. Many antitumor drugs are not ideal for the treatment of gliomas due to the blood-brain barrier. Temozolomide (TMZ) is a DNA alkylating agent that can cross the blood-brain barrier. As the only first-line chemotherapeutic drug for malignant gliomas at present, TMZ is widely utilized to provide a survival benefit; however, some patients are inherently insensitive to TMZ. In addition, patients could develop acquired resistance during TMZ treatment, which limits antitumor efficacy. To clarify the mechanism underlying TMZ resistance, numerous studies have provided multilevel solutions, such as improving the effective concentration of TMZ in tumors and developing novel small molecule drugs. This review discusses the in-depth mechanisms underlying TMZ drug resistance, thus aiming to provide possibilities for the establishment of personalized therapeutic strategies against malignant gliomas and the accelerated development and transformation of new targeted drugs.
Insights
Malignant gliomas are challenging to treat due to drug resistance. Understanding temozolomide (TMZ) resistance mechanisms is key to developing personalized therapies for brain tumors.
Area of Science:
- Neuro-oncology
- Cancer Pharmacology
Background:
- Malignant gliomas present significant diagnostic and therapeutic challenges due to their invasive nature, rapid progression, and poor prognosis.
- The blood-brain barrier restricts the efficacy of many antitumor drugs, necessitating agents that can penetrate this barrier.
- Temozolomide (TMZ), a DNA alkylating agent, is the current first-line chemotherapy for malignant gliomas, offering survival benefits but facing inherent and acquired resistance.
Purpose of the Study:
- To elucidate the complex mechanisms underlying temozolomide (TMZ) resistance in malignant gliomas.
- To explore strategies for overcoming TMZ resistance, including optimizing drug concentration and developing novel targeted therapies.
- To provide insights for developing personalized therapeutic strategies and accelerating new drug development for malignant gliomas.
Main Methods:
- This review synthesizes findings from numerous studies investigating TMZ resistance.
- Analysis of multilevel solutions proposed to combat TMZ resistance.
- Discussion of molecular mechanisms contributing to both intrinsic and acquired TMZ resistance.
Main Results:
- Identified inherent insensitivity and acquired resistance to TMZ as major limitations in malignant glioma treatment.
- Highlighted the need for strategies to improve effective TMZ concentration within tumors.
- Reviewed the development of novel small molecule drugs as potential alternatives or adjuncts to TMZ.
Conclusions:
- Understanding TMZ resistance mechanisms is crucial for advancing malignant glioma treatment.
- Personalized therapeutic strategies are essential to overcome drug resistance and improve patient outcomes.
- Further research into novel targeted drugs is necessary to enhance antitumor efficacy against resistant gliomas.
