Fill 15 years of domestic blanks! Global drug research advances on glioma from new treatment approval

Guide: Re-Ding Pharmaceutical Oncology Electric Field Treatment Ep Shield ® approved for listingRecently, Reding Pharmaceuticals announced that NMPA has approved the listing application for tumor electric field treatment of Epshield ® for the treatment of newly diagnosed glioblastoma patients with temomine, as well as as for the treatment of patients with recurrent glioblastoma as a single therapyat a time when "the first glioblastoma therapy in mainland China in 15 years has been approved", I think it is time to give an overview of the full picture of glioma and a summary of global drug progressBecause, brain glioma really with its special microenvironment, human beings in the road to fight cancer a major obstacle!brain gliomas - disease key information
glioma refers to tumors originating from glioblastoma cells of the brain, is the most common primary intracranial tumors; Ionizing radiation and high-pre-eclampsia genetic mutations associated with rare syndromes,WHO central nervous system tumor classification classified glioma synoda level I-IV, I, II as low-grade glioma, III, IV as high-level glioma,clinical manifestations mainly include intracranial pressure increase, neurofunctionandopathy and seizures 3 categoriesFigure 1: 2010-2014/The incidence of different types of glioma in the United States
brain gliomas , molecular markerstumor molecular markers, are chemicals that reflect the presence of tumorsThey are not present in normal adult tissue, or significantly increased in the amount of tumor tissue, their presence or change can indicate the nature of the tumor, so as to understand the tumor status to assist in guiding treatmentThe diagnosis of glioma requires the acquisition of specimens through tumor removal or biopsy, tissue and molecular pathology examination, and the determination of pathological classification and molecular subtypecurrent major molecular pathology markers include: isocitric acid dehydrogenase (IDH) mutation, chromosomal 1p/19q joint deletion state, O-6-methylintole-DNA methylpatoase promoter region methylation, alpha-thalassemia with reticutic syndrome X chain Gene mutation, telomerase reverse transcriptase promoter mutation, human othrole H3.3K27M mutation, BRAF gene mutation, PTPRZ1-MET gene fusion, miR-181d, metaopaicular reLA gene fusion, etcFigure 2:of the molecular diagnostic process for glioma stoma an insurmountable barrier - BBB a large number of new drugs used to treat central nervous system diseases often fail to pass clinical trials because they cannot cross the blood-brain barrier (Blood-Brain Barrier, BBB) Therefore, how to overcome BBB and increase the concentration of anti-tumor drugs in tumor tissue is very important to improve the efficacy of glioma patients the physiological protection function of BBB, making the delivery of drugs acting on the central nervous system into the brain becomeas a major problem Cerebral capillary endothelial cells are connected to each other by tightly connected proteins, forming a physical barrier with only limited window holes and cell drinking bubbles, allowing the passage of protokinesic drugs with a molecular weight of less than 400Da, preventing the entry of small molecules of protoplasmic drugs and macromolecules such as antibodies, antibodies-drug compounds A variety of transportproteins on BBB are also the main factors that inhibit drug entering the brain, and are the main reasons for the poor efficacy of the commonly used anti-tumor drugs paeppen, yewalcohol and polysoft stars on glioma The study found that BBB in patients with glioma was affected by pathological factors to some extent of damage, but there is still a complete BBB in the tumor area of the glioma, which can prevent the distribution of the active ingredients of the drug to tumor cells As a result, BBB can significantly affect the delivery of therapeutic drugs, thereby limiting efficacy Figure 3: BBB defense of glioma for example
drug treatment and chemotherapy as the main means
for high-level glioma, due to its growth and recurrence rate, active and effective personalized chemotherapy will be more valuable Other drug treatments include molecular target therapy, bioimmune therapy, etc among the , the chemotherapy drugs recommended by the high-level cerebral glioma guidelines are tamoxidamine, methylchom, lomoxin, Changchun xinbase, carmostine, ilitam, eposide, cisplatin, carp, cyclophosphamide, etc.; To temolymine, methylpyridine mainly recommended by the recurrence of cerebroglioma, methylzine, caplatinum, cisplatin, lomus, carmostin, bevalamono, ilibution, eposide etogin, cyclophosphamide; Figure 4: Brain glioma treatment process glioma - has been listed key drugs to introduce NO1- tamoxamine - glioma milestone drug pyrimozole, development company for Mersadon, in 1999 approved by the United States FDA listed, in recent years annual sales of about 200 million U.S dollars The species is a tetrapenacinator, easy to enter the blood-brain barrier, concentration in brain tissue can reach 30% to 40% of the blood concentration It has been widely used in the chemotherapy of central nervous system tumors, especially malignant gliomas, and has become a "milestone" in the progress of glioma chemotherapy Temoamine is absorbed quickly after oral administration, and bioavailability is nearly 100% Under physiological pH conditions, temolyne is rapidly converted into methyl trinitrogenneamide, which makes tumor cell DNA alkylation play its cytotoxic effect In the way of administration, temolymine is also developing towards multi-directional, the classic tamamine administration for oral administration, and is currently carrying out a variety of drug delivery pathways of drug development NO2 to Bevalbeek anti-
bevabezumab, the development company for gene Tek, in 2004 approved by the U.S FDA listed, is a recombinant monoclonal IgG antibody, can be specifically antagonistic VEGF, thereby reducing new angiogenesis, induced angiogenesis inhibited tumor growth; Currently, the drug's approved indications include breast cancer, cervical cancer, colorectal cancer, glioma, non-small cell lung cancer, ovarian cancer and renal cell carcinoma; glioma in the research and reserve drug at present, clinical III/II/I in the study of drugs used to treat glioma, 110, mainly concentrated in clinical phase II and clinical Phase I, into the clinical phase III varieties in about 10, the author believes that the clinical varieties of Phase III of concern for the new base company and Agios co-development of Vorasidenib, for the IDH inhibitors, and the variety at the same time to carry out biliary cancer, soft asarcoma and other clinical trials domestic, for glioma indications of drug development, mainly concentrated in clinical Phase I, the development company has Sichuan Hengkang, Zhengda Tianqing, Nanjing Edcheng, Shanghai Pharmaceutical Institute, Chenxin Pharmaceuticals, Dongsun medicine, first sound pharmaceutical, etc.; Table 1: Glioma Clinical Phase III in the study of drugs reference
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