Glioma is the most common primary tumor of the central nervous system, which develops mostly in young adults, is difficult to treat, and has a poor prognosis. In 2005, Stupp et al. demonstrated for the first time in a prospective randomized controlled study that concurrent radiotherapy with temozolomide and adjuvant chemotherapy with temozolomide could prolong the survival of patients with newly diagnosed glioblastoma, but the overall prognosis is still not optimistic, with a 5-year overall survival rate of 9% at long-term follow-up. The overall survival rate is 9.8%, which means that the majority of patients still have difficulty avoiding tumor recurrence and progression to death. Therefore, how to improve the outcome of glioma treatment and patient prognosis is still the direction of efforts in the field of neuro-oncology. Since surgical resection of tumor is the most direct and effective means to eliminate tumor, the degree of tumor resection is closely related to patient prognosis. However, due to the anatomical location and functional peculiarities of the brain, in order to maximize the extent of tumor removal while preserving neurological function, neurosurgeons have explored various techniques for precise tumor removal, such as neuronavigation, intraoperative fluorescence contrast technique to show the tumor, and intraoperative MRI to monitor whether the tumor is completely removed. However, the aggressive growth characteristics of glioma make it difficult to completely remove the tumor during surgery. Therefore, people look to post-surgical radiotherapy to kill the remaining tumor cells. Therefore, people have been devoted to exploring radiotherapy techniques that can effectively kill tumors without damaging brain function, such as CT 3D positioning, conformal intensity modulated radiotherapy, proton therapy, etc. Unfortunately, so far, the radiation therapy has not been effective in killing tumors. Unfortunately, to date, no large sample of clinical results have shown that advanced radiotherapy techniques can significantly improve the efficacy of glioma. Although gliomas are prone to local recurrence, they rarely metastasize distantly, so attempts have been made to improve the local control rate with local extended-release chemotherapy, represented by BCNU extended-release tablets, which have been available in the United States for many years; however, their clinical benefit is also limited, and this product is not yet available in China. A question to ponder is why intense local treatment, or local recurrence? Recent studies have suggested that the presence of glioma stem cells may be the root cause of recurrent glioma recurrence. Therefore, systemic treatment, especially treatment targeting glioma stem cells, may be the hope for a complete cure of glioma. Chemotherapy is the traditional systemic treatment, and the application of temozolomide is a milestone in glioma chemotherapy, giving a ray of hope for glioma chemotherapy. However, clinical results are still unsatisfactory due to dose-limiting toxicity and drug resistance. Therefore, overcoming drug resistance and exploring effective new drugs have become another hot topic to improve the effectiveness of glioma treatment. Breakthroughs in drug resistance research It was found that only glioblastoma patients with methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter benefited from radiotherapy combined with temozolomide chemotherapy, while patients lacking methylation did not have an extended survival time. MGMT has been shown to be a more certain indicator associated with resistance to nitrosoureas and temozolomide in malignant gliomas, and can be helped to overcome resistance by combination, altered dosing and pseudo-substrate inactivation of MGMT. Among them, changing the conventional dosing of temozolomide is one of the hot spots of glioma chemotherapy research in recent years. The conventional usage of temozolomide is 150-200 mg /m2/d for 5 days; however, the conventional 5-day regimen is not easy to overcome the resistance caused by MGMT. In the literature, it has been reported that the dose intensity of temozolomide is 1.5-2.0 times higher than that of the standard 5-day regimen when using a dose-intensive dosing regimen such as temozolomide alternating weekly or continuous 21-day dosing regimen, and the O6-methyl guanine formed by the interaction between temozolomide and cellular DNA is repaired by MGMT, thus depleting MGMT to overcome the drug resistance itself. A continuous 21-day regimen (temozolomide 75 mg/m2 d1-21, repeated every 28 days) was used to treat 33 patients with recurrent glioblastoma who had not been previously treated with chemotherapy, with an objective efficiency of 9%, a progression-free survival rate of 30.3% at 6 months, and a median survival time of 40 weeks. In addition, rechemotherapy with a modified temozolomide regimen for malignant gliomas that have progressed after previous conventional temozolomide chemotherapy/radiotherapy remains effective, and in the RESCUE study, patients with mesenchymal astrocytoma and glioblastoma that had progressed after previous conventional temozolomide chemotherapy/radiotherapy were treated with temozolomide 50 mg/m2/d for 1 year or until tumor progression, the 6-month progression-free survival rates were 35.7% and 23.9%, respectively. In recent years, good results in MGMT-positive tumors have been reported in the literature using interferon in combination with temozolomide for the treatment of gliomas. Molecular targeted therapy shows promise Malignant glioma is essentially a polygenic abnormal disease, and its occurrence, development and therapeutic resistance are the result of abnormal activation of multiple intracellular signaling pathways. In recent years, molecularly targeted therapies targeting cellular receptors, key genes and regulatory molecules have become a hot topic in tumor treatment and are expected to provide effective new approaches for clinical cure of glioma. Many molecularly targeted drugs with different mechanisms have entered clinical trials for glioma, such as tyrosine kinase inhibitors, vascular endothelial growth factor/receptor inhibitors, epidermal growth factor receptor inhibitors, farnesyl transferase inhibitors, mTOR inhibitors, matrix metalloproteinase inhibitors, histone deacetylase inhibitors, protein kinase C inhibitors, etc. Bevacizumab: Malignant glioma is a highly vascularized solid tumor. in 2007, a phase II clinical study completed at Duke University used bevacizumab in combination with irinotecan to treat 32 cases of recurrent malignant glioma with an overall objective efficiency of 63% and a median progression-free survival of 23 weeks and a median survival of 40 weeks for patients with glioblastoma. in 2009, Friedman et al. further compared the efficacy and toxicity of two regimens of bevacizumab alone and bevacizumab in combination with irinotecan. 167 patients with recurrent glioblastoma randomized to bevacizumab alone or in combination with irinotecan had 6-month progression-free survival rates of 42.6% and 50.3%, respectively, objective efficiency rates of 28.2% and 37.8%, respectively, and median survival Kreisl et al. treated 48 patients with recurrent glioblastoma with bevacizumab alone followed by bevacizumab in combination with irinotecan after tumor progression, with an objective efficiency of 35%, median progression-free survival of 16 weeks, 6-month progression-free survival of 29%, and median OS of 31 weeks. Currently, the NCCN Clinical Practice Guidelines for Oncology recommend bevacizumab alone or in combination with irinotecan for recurrent high-grade glioma. Cilengitide: The aggressive characteristics of glioblastoma are closely related to tumor recurrence. Cilengitide is an integrin inhibitor, and in vitro studies have shown synergistic effects of cilengitide with radiation and chemotherapy. Recently, a multicenter phase I/II clinical trial evaluated the efficacy and safety of concurrent radiotherapy and adjuvant chemotherapy with cilengitide in newly diagnosed glioblastoma patients treated with standard temozolomide. 52 patients enrolled had a median progression-free survival of 8 months, a median survival of 16.1 months, and a 2-year survival rate of 35%. progression-free survival and overall survival in patients with MGMT promoter methylation ( 13.4 months and 23.2 months) were longer (3.4 months and 13.1 months) than in patients with MGMT promoter non-methylation. Compared to historical controls, cilengitide + temozolomide concurrent and adjuvant chemotherapy showed improved outcomes in patients with glioblastoma methylated at the MGMT promoter. Nitrozumab: Amplification and overexpression of the epidermal growth factor receptor (EGFR) gene is present in 40% of glioblastomas. A clinical phase I/II study using nitrozumab in combination with radiotherapy for the treatment of adult malignant glioma had an objective efficiency of 37.9% and a disease stabilization rate of 41.4%, and the presence of radioactive selective clustering of 99mTc-labeled nitrozumab at residual sites of intracranial lesions was detected by immunoimaging. It is an orphan drug for advanced glioma. The Department of Neuro-Oncology of the Cancer Hospital of Sun Yat-sen University is currently conducting a clinical study of nitrozumab in combination with temozolomide for the treatment of recurrent malignant glioma, which has shown good objective efficacy in some patients. It is noteworthy that the results of a study published by Mellinghoff et al. in the New England Journal of Medicine in 2005 found that EGFR gene amplification was not associated with clinical efficacy, while combined expression of EGFRvIII and PTEN was significantly and positively associated with clinical efficacy. This suggests that in order to further improve the clinical efficacy of molecularly targeted drugs, it is necessary to conduct in-depth molecular genetic studies to find molecular indicators that may predict efficacy and to screen for sensitive populations that can truly benefit from molecularly targeted therapy.