Lomustine and nimustine exert efficient antitumor effects against glioblastoma models with acquired temozolomide resistance

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve overall survival, free-progression survival, and life quality in glioblastoma patients. (2) Methods: Our objective is to recap the actual state-of-the-art in glioblastoma treatment, resume the actual research and future perspectives on immunotherapy, as well as the new synthetic molecules and natural compounds that represent potential future therapies at preclinical stages. (3) Conclusions: Despite the great efforts in therapeutic research, glioblastoma management has suffered minimal changes, and the prognosis remains poor. Combined therapeutic strategies and delivery methods, including immunotherapy, synthetic molecules, natural compounds, and glioblastoma stem cell inhibition, may potentiate the standard of care therapy and represent the next step in glioblastoma management research.

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“…As a result of its lipo-solubility, it easily crosses the BBB, making it a viable candidate for treating intrinsic brain cancers [38,40].…”

Section: Chemotherapy: Temozolomide (Tmz)mentioning

confidence: 99%

Glioblastoma Treatment: State-of-the-Art and Future Perspectives

Camacho

Flores-Vázquez

Moscardini-Martelli

et al. 2022

IJMS

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“…Nitrosourea chemotherapeutic drugs have been applied for the treatment of gliomas before the emergence of TMZ ( 81 ). Over the past decade, previous studies have shown that nitrosourea chemotherapy can be used for the remedial treatment of TMZ resistance ( 85 ).…”

Section: Nitrosourea-based Chemotherapymentioning

confidence: 99%

Research progress of anti-glioma chemotherapeutic drugs (Review)

et al. 2022

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Glioma is the most common primary intracranial malignancy in the central nervous system. At present, the most important treatment option is surgical resection of the tumor combined with radiotherapy and chemotherapy. The principle of operation is to remove the tumor to the maximal extent on the basis of preserving brain function. However, prominent invasive and infiltrative proliferation of glioma tumor cells into the surrounding normal tissues frequently reduces the efficacy of treatment. This in turn worsens the prognosis, because the tumor cannot be completely removed, which can readily relapse. Chemotherapeutic agents when applied individually have demonstrated limited efficacy for the treatment of glioma. However, multiple different chemotherapeutic agents can be used in combination with other treatment modalities to improve the efficacy while circumventing systemic toxicity and drug resistance. Therefore, it is pivotal to unravel the inhibitory mechanism mediated by the different chemotherapeutic drugs on glioma cells in preclinical studies. The aim of the present review is to provide a summary for understanding the effects of different chemotherapeutic drugs in glioma, in addition to providing a reference for the preclinical research into novel chemotherapeutic agents for future clinical application.

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“…As alkylating agents with broad-spectrum antitumour activity, nitrosourea drugs may penetrate the BBB due to their nonionic properties and high lipid solubility. Nitrosourea drugs alkylate tumour cell DNA at multiple sites, inducing the formation of DNA crosslinking and the occurrence of single-strand or double-strand breaks, inhibiting DNA repair and ultimately altering the structure of DNA and proteins ( 61 , 62 ). Various miRNAs have been reported to be related to nitrosourea resistance in gliomas ( Table III ).…”

Section: Mirnas and Glioma Drug Resistancementioning

confidence: 99%

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

et al. 2022

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As the most common primary tumour of the central nervous system, gliomas have a high recurrence rate after surgical resection and are resistant to chemotherapy, particularly high-grade gliomas dominated by glioblastoma multiforme (GBM). The prognosis of GBM remains poor despite improvements in treatment modalities, posing a serious threat to human health. At present, although drugs such as temozolomide, cisplatin and bevacizumab, are effective in improving the overall survival of patients with GBM, most patients eventually develop drug resistance, leading to poor clinical prognosis. The development of multidrug resistance has therefore become a major obstacle to improving the effectiveness of chemotherapy for GBM. The ability to fully understand the underlying mechanisms of chemotherapy resistance and to develop novel therapeutic targets to overcome resistance is critical to improving the prognosis of patients with GBM. Of note, growing evidence indicates that a large number of abnormally expressed noncoding RNAs (ncRNAs) have a central role in glioma chemoresistance and may target various mechanisms to modulate chemosensitivity. In the present review, the roles and molecular mechanisms of ncRNAs in glioma drug resistance were systematically summarized, the potential of ncRNAs as drug resistance markers and novel therapeutic targets of glioma were discussed and prospects for glioma treatment were outlined. ncRNAs are a research direction for tumor drug resistance mechanisms and targeted therapies, which not only provides novel perspectives for reversing glioma drug resistance but may also promote the development of precision medicine for clinical diagnosis and treatment.

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Lomustine and nimustine exert efficient antitumor effects against glioblastoma models with acquired temozolomide resistance

Cited by 17 publications

References 56 publications

Glioblastoma Treatment: State-of-the-Art and Future Perspectives

Glioblastoma Treatment: State-of-the-Art and Future Perspectives

Research progress of anti-glioma chemotherapeutic drugs (Review)

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

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