Core tip: Drugs currently in the clinic for the treatment of glioma include: monoclonal antibodies against molecular targets such as bevacizumab and cetuximab; EGFR tyrosine kinase inhibitors and VEGF tyrosine kinase inhibitors such as Cediranib and Lapatinib, as well as serine-threonine kinase inhibitors Enzastaurin, integrin antagonist cilengitide, etc. Malignant glioma treatment has been one of the most difficult research topics in the field of neurosurgery, accounting for about 50% of the incidence of primary intracranial tumors and killing nearly 600,000 young and middle-aged people worldwide each year. The combined age of onset peaks at 30-40 years old, or 10-20 years old. Gliomas in the cerebral hemisphere account for 51.4% of all gliomas, with astrocytomas being the most common, followed by glioblastomas and oligodendrogliomas. The ventricular system also accounts for 23.9% of all gliomas, mainly tubulointerstitial tumors, medulloblastomas, and astrocytomas, while cerebellar gliomas account for 13% of all gliomas, mainly astrocytomas. The clinical manifestations of malignant glioma are mainly headache, nausea, vomiting and visual impairment. Other symptoms include epilepsy, vertigo, adductor nerve palsy, and behavioral and personality changes. Traditionally, the chemotherapeutic agents of choice for malignant brain tumors are the nitrosoureas, such as carmustine (BCNU) and lomustine (CCNU). Their non-ionic properties and high lipid solubility make them easy to penetrate the blood-brain barrier. Carmustine (BCNU) is the most widely used chemotherapeutic agent for brain tumors. It is fat-soluble and has low molecular weight, which can cross the blood-brain barrier and is broken down into two active components in the body, one with carbamylation activity and one with alkylation. It causes alkylation of the oxygen atom at position 6 of guanine on DNA. It causes cross-linking of DNA strands, which affects DNA replication and kills tumor cells: it also has more binding sites, which makes it easy to work when administered locally at higher concentrations. A series of serious complications can occur at accumulation doses above 1400 mg. These include delayed hematopoietic suppression, hepatotoxicity, and pulmonary fibrosis.f21 In response to these problems, many scholars have conducted a number of useful studies on the mode and route of administration of carmustine in order to improve the efficacy of chemotherapy and enhance the quality of patient survival. It has been found that extended-release formulations can significantly reduce the toxic side effects of carmustine (BCNU) and prolong survival. Temozolomide is the only oral chemotherapy drug approved by FDA for the treatment of malignant glioma. Temozolomide (TMZ) is a second-generation alkylating chemotherapeutic agent. It acts directly on the substrate for DNA synthesis, causing methylation, which leads to DNA single- and double-strand breaks, inhibits DNA replication, and finally leads to cell death. In 1999, the FDA approved TMZ for chemotherapy of relapsed malignant astrocytoma, and in March 2005, the FDA approved it for the treatment of new glioblastoma patients. In March 2005, the FDA approved TMZ for the treatment of new patients with glioblastoma. In Europe, TMZ is approved for relapsed malignant astrocytoma and glioblastoma. In a review in the New England Journal, national experts described temozolomide as “ushering in a new era of chemotherapy for brain tumors” and “a milestone in chemotherapy for brain tumors. According to the data provided by MINE, the domestic market share of temozolomide reached RMB 60 million in 2010, representing a growth rate of 50% compared to 2009. From the sales data of 2008 to 2010, the annual relative average growth rate of temozolomide in China is around 40%. The main manufacturers of temozolomide are Tianjin Tianshi Li Pharmaceutical, Finland Orin Pharmaceutical and Schering-Plough Pharmaceutical. In 2010, the domestic market share of temozolomide of these three companies was 52.75%, 35.81% and 11.44% respectively. Anti-angiogenic therapy Research shows that malignant glioma is also a highly vascularized solid tumor, so in recent years, foreign scholars have made many attempts in anti-angiogenic therapy for malignant glioma, including thalidomide and bevacizumab. Among them, a phase II clinical study of bevacizumab combined with irinotecan (CPT-11) for the treatment of recurrent malignant glioma completed at Duke University Brain Tumor Center in the United States showed encouraging data, with an overall objective efficiency of 63%, median PFS of 23 weeks, 6-month PFS rates of 30% and 56% in grade IV and III gliomas, respectively, and overall median survival of 40 weeks. Based on the results of this study, the 2009 NCCN Clinical Practice Guidelines for Oncology recommended bevacizumab alone or in combination with CPT-11 as one of the salvage treatment options for recurrent high-grade gliomas. In 2009, the FDA approved bevacizumab (Avastin) for use in patients with glioblastoma multiforme (GBM) whose disease continues to deteriorate despite conventional treatment conditions. Drugs currently in the clinic for the treatment of glioblastoma include: monoclonal antibodies against molecular targets such as bevacizumab and cetuximab; EGFR tyrosine kinase inhibitors and VEGF tyrosine kinase inhibitors such as Cediranib and Lapatinib, as well as serine-threonine kinase inhibitors Enzastaurin Enzastaurin, integrin antagonist Cilengitide, etc. Enzastaurin was approved by the EU and FDA in 2006 as a rare disease drug for glioblastoma multiforme. The results of a phase II trial of the drug in recurrent glioblastoma multiforme were published in the American Society of Clinical Oncology. Enzastaurin was well tolerated in 92 patients with a response rate of 20-25% with 500 mg daily, and the most common side effect was reduced platelets. It reduces cancer cell survival by inhibiting the PKC-B and PI3 kinase/AKT pathways. Phase III clinical studies of this drug are ongoing. Cilengitide An independent phase II study in newly diagnosed patients with glioblastoma multiforme (GBM) showed that cilengitide in combination with chemoradiotherapy (combined and adjuvant temozolomide plus radiotherapy) may prolong survival. Cilengitide is in phase III clinical development as the first integrin-inhibiting factor antitumor agent. It targets the tumor and the blood supply structures that provide nutrition to the tumor and promote the growth of cancer cells. The primary endpoint of the phase II clinical study of cilengitide showed a trend towards higher overall survival in the cilengitide 2000 mg treatment group than in the 500 mg group. Median patient survival was 18.9 months (95% CI 16.6C21.9) and overall survival at 12-month follow-up was 79.5% (95% CI 71C87). Dr. Wolfgang Wein, Executive Vice President, Group Oncology, Merck Sharp & Dohme, said cilengitide has the potential to treat this devastating disease.