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DNA inhibitors for the treatment of brain tumors
Lucia Lisi1, Marta Chiavari1, Gabriella Maria Pia Ciotti1
1Department of Safety and Bioethics, Catholic University Medical School, Rome, Italy.
Abstract:
Introduction: The worldwide incidence of central nervous system (CNS) primary tumors is increasing. Most of the chemotherapeutic agents used for treating these cancer types induce DNA damage, and their activity is affected by the functional status of repair systems involved in the detection or correction of DNA lesions. Unfortunately, treatment of malignant high-grade tumors is still an unmet medical need.Areas covered: We summarize the action mechanisms of the main DNA inhibitors used for the treatment of brain tumors. In addition, studies on new agents or drug combinations investigated for this indication are reviewed, focusing our attention on clinical trials that in the last 3 years have been completed, terminated or are still recruiting patients.Expert opinion: Much still needs to be done to render aggressive CNS tumors curable or at least to transform them from lethal to chronic diseases, as it is possible for other cancer types. Drugs with improved penetration in the CNS, toxicity profile, and activity against primary and recurrent tumors are eagerly needed. Targeted agents with innovative mechanisms of action and ability to harness the cells of the tumor microenvironment against cancer cells represent a promising approach for improving the clinical outcome of CNS tumors.
Insights
This review covers DNA-damaging chemotherapy for brain tumors, highlighting challenges in treating high-grade gliomas. New agents and clinical trials offer hope for improved outcomes in central nervous system (CNS) cancer treatment.
Area of Science:
- Neuro-oncology
- Cancer Chemotherapy
- DNA Damage and Repair
Background:
- Central nervous system (CNS) primary tumors incidence is rising globally.
- Current chemotherapeutic agents for CNS tumors induce DNA damage, with efficacy dependent on DNA repair pathways.
- Malignant high-grade brain tumors remain a significant unmet medical need.
Purpose of the Study:
- To review the mechanisms of action of primary DNA inhibitors used in brain tumor treatment.
- To summarize recent clinical trials (last 3 years) of novel agents and drug combinations for CNS tumors.
- To provide an expert opinion on future directions in CNS tumor therapy.
Main Methods:
- Literature review of DNA inhibitors and their mechanisms.
- Analysis of clinical trial data for CNS tumor treatments within the last three years.
- Synthesis of expert opinion on therapeutic strategies.
Main Results:
- Established DNA inhibitors are central to current brain tumor chemotherapy.
- Ongoing clinical trials are exploring new agents and combinations with varying outcomes.
- Significant progress is needed to improve drug efficacy and delivery for CNS malignancies.
Conclusions:
- Aggressive CNS tumors require novel therapeutic strategies for improved outcomes.
- Development of agents with enhanced CNS penetration, better toxicity profiles, and activity against recurrent tumors is crucial.
- Targeted therapies and modulation of the tumor microenvironment show promise for future CNS cancer treatment.
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