A targeted toxin, also known as an immunotoxin or cytotoxin, is a cellular molecule that binds to a specific antigen or receptor on the surface of tumor cells or tumor vascular endothelial cells, such as epidermal growth factor receptor, transferrin receptor, interleukin-13 or interleukin-4 receptor, and whose toxin component kills tumor cells. Antibodies for the treatment of malignant tumors have gradually evolved from murine-derived and chimeric antibodies to humanized antibodies. Malignant brain tumors such as Glioblastoma Multiforme (GBM) are highly lethal tumors, and the average survival time after diagnosis of GBM is only about 14 months even with the combination of surgery, radiotherapy and chemotherapy. Experiments have shown that targeted toxins are highly cytotoxic to GBM cell lines; tumor-bearing animals treated with targeted toxins can prolong their lives or cause tumor regression. In clinical trials to date, targeted toxins have not shown significant neurotoxicity, and relevant tests have shown good therapeutic effects. 1. Toxins The most commonly used toxins in research are diphtheria toxin, Pseudomonas exotoxin, ricin and so on. They are derived from bacteria or plants, after hundreds of years of natural selection, a small amount of toxin can produce a large toxic effect. Diphtheria toxin (DT) and Pseudomonas aeruginosa exotoxin A (PE) have different structures and origins, but once they bind to specific antigens or receptors on the cell surface, both can play their role in inhibiting protein synthesis through endocytosis or inclusion body transport into the cell . A single toxin molecule can kill a tumor cell, while current chemotherapy requires 105 molecular weight drugs to achieve this purpose. 2. Experimental studies of toxin therapy for brain tumors The anticancer ability of immunotoxins was recognized in a series of studies of hematologic cancers as early as 1970, but it was not until 1987 that studies of immunotoxin therapy for brain tumors were reported. The first generation of immunotoxins were immunotoxins prepared by monoclonal antibodies against an antigenic molecule on the surface of tumor cells. The disadvantages of poor stability, immunogenicity, and poor penetration led to the therapeutic effect of the toxin in vivo being far from as efficacious as in vitro experiments. The second generation of toxins is the application of genetic engineering recombinant technology to clone and recombine the genes encoding the toxins with the ligand genes of tumor cell surface specific molecules, and then the chimeric toxins expressed in bacteria with high efficiency, the in vitro experimental results are exciting and clinical experiments are emerging. 3. Problems and perspectives of targeted toxin therapy for brain tumors Immunotoxins have positive clinical results for the treatment of hematologic malignancies, while the treatment of solid tumors, including GBM, remains unsatisfactory [2,25]. It is generally believed that solid tumor cells such as GBM are less accessible to toxins than tumor cells in the blood and bone marrow is one of the possible reasons for the therapeutic differences. Currently, the following major issues should be considered when targeting toxins for the treatment of brain tumors. First, the specificity of the toxin is a prerequisite for targeted therapy, which depends on the specificity of the vector used, such as antibodies or cellular molecules. In the future, in addition to continuing research on finding tumor-specific markers, it is still important to take full advantage of the fact that some molecules on the surface of tumor cells are quantitatively vastly different compared to normal cells to explore tumor-targeted toxin therapeutic pathways. Secondly, toxin is an exogenous antigen with immunogenic properties. Patients with hematologic cancers may receive multiple toxin treatments without antibody production because of their impaired immune systems; whereas patients with solid tumors may produce antibodies against the toxin itself because of their largely normal immune systems affecting the efficacy [2,25]. However, how to maintain or enhance the toxin’s virulence while reducing its immunogenicity is also an important direction for future research. Again, how do toxins enter solid tumor tissue? The mode of toxin delivery, such as intra-arterial, intracerebroventricular delivery or the currently more commonly used CED modality, will remain one of the future research directions. In conclusion, although there are still some problems in the treatment of brain tumors with targeted toxins, they have shown potential clinical application. With the in-depth research on protein and genetic engineering technologies and intracranial drug delivery methods, targeted toxins will probably become an effective means to treat intracranial malignant tumors in addition to surgery, radiotherapy and chemotherapy.