Application of Nedissertib in treatment of spinal glioma

Abstract

The invention provides an application of Nedissertib in treatment of spinal cord glioma. According to the application, it is found for the first time that Nedissertib can inhibit growth of spinal glioma cells, it is found through combined radiotherapy that the growth of the spinal glioma cells can be more significantly inhibited through combination of Nedissertib and radiotherapy, and these findings highlight the treatment value of Nedissertib in spinal tumor, especially the value of Nedissertib in sensitization of radiotherapy. A new thought is provided for the treatment of the spinal glioma.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and specifically relates to the application of Nedisertib in treating spinal cord glioma. Background Art

[0002] Intramedullary spinal cord tumor (IMSCT) is a relatively rare malignant tumor in the central nervous system, accounting for about 4-10% of central nervous system tumors. Intramedullary spinal cord glioma originates from the spinal cord ectoderm and accounts for about 80% of intramedullary spinal cord tumors. There are usually no obvious symptoms in the early stage of spinal cord glioma, and when it can be detected by medical means, the tumor has grown to a considerable size. Spinal cord gliomas can compress the spinal cord in the spinal cord, causing neurological dysfunction, and in severe cases, death. Due to the special location, surgical resection is still the preferred treatment option at present, but because spinal cord gliomas are very small and invasive, the operation is very difficult. If the resection range is too large, spinal cord function damage will lead to serious consequences such as paralysis and incontinence. High-position cervical spinal cord intramedullary surgery may cause dyspnea or even death; if the resection range is small, the tumor tissue cannot be completely removed, and the residual tumor cells infiltrating into the spinal cord parenchyma will cause recurrence of spinal cord glioma. Radiotherapy as an adjuvant treatment for spinal cord glioma has always been controversial. Some studies believe that radiotherapy will aggravate spinal cord injury and cause serious spinal cord complications, and the scars formed at the lesion site after radiotherapy will affect secondary surgery.

[0003] Therefore, finding a new drug for treating spinal cord glioma is of vital importance in this field. Summary of the invention

[0004] To make up for the deficiencies of the prior art, the present invention provides the use of Nedisertib in treating spinal cord glioma.

[0005] To achieve the above purpose, the present invention adopts the following technical solution.

[0006] The first aspect of the present invention provides the use of Nedisertib in preparing a pharmaceutical composition for treating spinal cord glioma.

[0007] Furthermore, the spinal cord glioma is a mutant spinal cord glioma.

[0008] Furthermore, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

[0009] The second aspect of the present invention provides the use of Nedisertib in preparing a pharmaceutical composition for sensitizing spinal cord glioma to radiotherapy.

[0010] Furthermore, the spinal cord glioma is a mutant spinal cord glioma.

[0011] Furthermore, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

[0012] Furthermore, the pharmaceutical composition also includes other drugs / other radiosensitizers for treating spinal cord glioma.

[0013] Furthermore, the other drugs for treating spinal cord glioma include methotrexate, cytarabine, palbociclib, temozolomide, and doxorubicin.

[0014] Furthermore, the other radiosensitizers include metronidazole, misonidazole, nitroimidazole, benzamide, nicotinamide, cisplatin, mitomycin, tenizamine, nitrosoureas, and mercaptopurine.

[0015] Furthermore, the pharmaceutical composition also includes pharmaceutically acceptable excipients.

[0016] Furthermore, the pharmaceutically acceptable excipients include diluents, binders, surfactants, humectants, adsorption carriers, lubricants, fillers, and disintegrants.

[0017] Furthermore, the dosage form of the pharmaceutical composition includes solutions, tablets, powders, suspensions, emulsions, granules, capsules, pills, inhalants, gels, suppositories, creams, jellies, and sprays.

[0018] The third aspect of the present invention provides a pharmaceutical composition for treating spinal cord glioma / radiotherapy sensitization of spinal cord glioma, wherein the pharmaceutical composition comprises Nedisertib.

[0019] Furthermore, the spinal cord glioma is a mutant spinal cord glioma.

[0020] Furthermore, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

[0021] The fourth aspect of the present invention provides a method for inhibiting the growth of spinal cord glioma cells in vitro, the method comprising administering Nedisertib.

[0022] Furthermore, the spinal cord glioma is a mutant spinal cord glioma.

[0023] Furthermore, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

[0024] Furthermore, the method is a non-therapeutic method.

[0025] Advantages and beneficial effects of the present invention:

[0026] This application discovered for the first time that Nedisertib can inhibit the growth of spinal cord glioma cells. Through combined radiotherapy, it was found that Nedisertib combined with radiotherapy can more significantly inhibit the growth of spinal cord glioma cells. These findings highlight the therapeutic value of Nedisertib in spinal cord tumors, especially its value in sensitizing to radiotherapy, and provide new ideas for the treatment of spinal cord gliomas.

[0027] Biomaterial Deposit Information

[0028] SCA-S02:

[0029] Scientific description: human cells; depository: General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC); deposit address: No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45809.

[0030] SCA-S09:

[0031] Scientific description: human cells; depository: General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC); deposit address: No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45810.

[0032] SCA-S10:

[0033] Scientific description: human cells; depository: General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC); deposit address: No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45811.

[0034] SCA-S12:

[0035] Scientific description: human cells; depository: General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC); deposit address: No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45812.

[0036] SCA-S41:

[0037] Scientific description: human cells; depository: General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC); deposit address: No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45813. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 This is a diagram of the gene mutations in spinal cord glioma cells;

[0039] Figure 2 This is a graph showing the sensitivity of spinal cord glioma cells to Nedisertib;

[0040] Figure 3 This is a graph measuring the sensitivity of spinal cord glioma cells to the combination of Nedisertib and radiotherapy;

[0041] Figure 4 This is a live fluorescence imaging of spinal cord glioma cells in mice;

[0042] Figure 5 This is a graph of the growth curve of spinal cord glioma cells in mice;

[0043] Figure 6 This is a survival curve of mice after spinal cord glioma cells were implanted into mice;

[0044] Figure 7 This is a graph showing the inhibitory effect of anti-tumor drugs on spinal cord glioma cells SCA_S02;

[0045] Figure 8 This is a diagram showing the inhibitory effect of anti-tumor drugs on spinal cord glioma cells SCA_S09. DETAILED DESCRIPTION

[0046] The definitions of some terms used in this specification are provided below. Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0047] The present invention provides the use of Nedisertib in preparing a pharmaceutical composition for treating spinal cord glioma.

[0048] In some embodiments, Nedisertib (M3814) also includes pharmaceutically acceptable salts, solvates, and co-crystals of Nedisertib.

[0049] In some embodiments, pharmaceutically acceptable salts are preferably derived from inorganic or organic acids and bases. Such acid salts include, but are not limited to, the following: acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, lucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonic acid Salts, nicotinates, oxalates, pamoates, pectinates, persulfates, 3-phenyl-propionates, picrates, pivalates, propionates, succinates, tartrates, thiocyanates, toluenesulfonates, undecanoates, hydrohalides (e.g., hydrochlorides and hydrobromides), sulfates, phosphates, nitrates, sulfamates, malonates, salicylates, methylene-bis-b-hydroxynaphthoates, gentisates, isethionates, di-p-toluoyl tartrates, ethanesulfonates, cyclohexylsulfamates, quinates, and the like. Pharmaceutically acceptable base addition salts include, but are not limited to, those derived from alkali metal or alkaline earth metal bases or conventional organic bases, such as triethylamine, pyridine, piperidine, morpholine, N-methylmorpholine, ammonium salts, alkali metal salts (such as sodium and potassium salts), alkaline earth metal salts (such as calcium and magnesium salts), salts with organic bases (such as dicyclohexylamine salts, N-methyl-D-glucamine), and salts with amino acids such as arginine, lysine.

[0050] In some embodiments, a solvate refers to an association or complex of one or more solvent molecules with a compound of Nedisertib. Examples of solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide (DMSO), ethyl acetate, acetic acid, acetonitrile, and ethanolamine. Hydrate refers to a complex in which the solvent molecule is water.

[0051] In some embodiments, a co-crystal refers to a crystal structure containing at least two different compounds that are solids in pure form under ambient conditions. Co-crystals are made from neutral molecular species, and all species remain neutral after crystallization. Preferably, a co-crystal is a crystalline homogeneous material in which two or more building compounds are present in a defined stoichiometric ratio.

[0052] The pharmaceutical composition also includes pharmaceutically acceptable excipients.

[0053] In some embodiments, a pharmaceutically acceptable excipient is used to refer to a material that is compatible with a recipient, preferably a mammal, more preferably a human, and is suitable for delivering an active agent to a target site without terminating the activity of the agent. Toxicity or side effects (if any) associated with the pharmaceutically acceptable excipient are preferably commensurate with a reasonable risk / benefit ratio for the intended use of the active agent.

[0054] In some embodiments, pharmaceutically acceptable excipients include but are not limited to diluents, adhesives, surfactants, humectants, adsorption carriers, lubricants, fillers, and disintegrants. These pharmaceutically acceptable excipients are used to help the stability of the formulation or to help improve the activity or its biological effectiveness or to produce an acceptable taste or smell in the case of oral administration. The preparations that can be used in such pharmaceutical compositions can be in the form of the original compound itself or optionally in the form of its pharmaceutically acceptable salt. The pharmaceutical composition thus prepared can be administered in any appropriate manner known to those skilled in the art as needed.

[0055] Among them, the diluent includes but is not limited to lactose, sodium chloride, glucose, urea, starch, and water.

[0056] Binders include, but are not limited to, starch, pregelatinized starch, dextrin, maltodextrin, sucrose, gum arabic, gelatin, methylcellulose, carboxymethylcellulose, ethylcellulose, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, alginic acid and alginates, xanthan gum, hydroxypropyl cellulose and hydroxypropyl methylcellulose.

[0057] Surfactants include, but are not limited to, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, and cetyl alcohol.

[0058] Humectants include, but are not limited to, glycerin.

[0059] Adsorption carriers include, but are not limited to, bentonite, silica gel, kaolin, and bentonite.

[0060] Lubricants include, but are not limited to, zinc stearate, glyceryl monostearate, polyethylene glycol, talc, calcium and magnesium stearate, polyethylene glycol, boric acid powder, hydrogenated vegetable oil, sodium stearyl fumarate, polyoxyethylene monostearate, monolauric sucrose ester, sodium lauryl sulfate, magnesium lauryl sulfate, and magnesium dodecyl sulfate.

[0061] Fillers include, but are not limited to, mannitol (granular or powdered), xylitol, sorbitol, maltose, erythrose, microcrystalline cellulose, polymeric sugars, coupling sugars, glucose, lactose, sucrose, dextrin, starch, sodium alginate, laminarin powder, agar powder, calcium carbonate, and sodium bicarbonate.

[0062] Disintegrants include, but are not limited to, cross-linked vinyl pyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl methyl, cross-linked sodium carboxymethyl cellulose, and soybean polysaccharides.

[0063] In some embodiments, the pharmaceutical compositions described above may be administered to a subject by any convenient route of administration (whether systemically / peripherally or at the site of desired action), including, but not limited to, one or more of the following: oral (e.g., as a tablet, capsule, or as an ingestible solution), topical (e.g., transdermal, intranasal, ocular, buccal, and sublingual), parenteral (e.g., using injection techniques or infusion techniques, and including, for example, by injection (e.g., subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcutaneous, intraarticular, subarachnoid, or intrasternal), for example, implantation of a depot (e.g., subcutaneously or intramuscularly), pulmonary (e.g., by inhalation or insufflation therapy, through the mouth or nose using, for example, an aerosol), gastrointestinal.

[0064] In some embodiments, the pharmaceutical composition can be manufactured by methods well known in the art, such as conventional granulation, mixing, dissolution, encapsulation, lyophilization or emulsification, etc. The pharmaceutical composition can be prepared in various forms, including but not limited to solutions, tablets, powders, suspensions, emulsions, granules, capsules, pills, inhalants, gels, suppositories, creams, jellies, and sprays.

[0065] In some embodiments, pharmaceutical composition will change according to the desired effect.Therefore, the optimal content of the pharmaceutical composition of the present application can be easily determined by those skilled in the art, and can be adjusted according to the following various factors: the type and severity of the disease, the content of other components contained in the pharmaceutical composition, the type of preparation, the age, body weight, general health, sex and diet of the patient, the time of application, the route of administration, the secretion rate of the drug, the duration of treatment and the drug used simultaneously.The amount of the pharmaceutical composition should be determined considering the factors, and it can be applied once a day or in several portions.However, it should be understood that the actual dose of the active ingredient should be determined considering various relevant factors, including the disease treated, the severity of the disease, the route of application and the weight, age and sex of the patient.Therefore, dosage does not limit the scope of the application in any way.

[0066] In some embodiments, treatment refers to clinical intervention that attempts to alter the natural course of the individual being treated, and can be performed for prevention or during clinical pathology. Desirable therapeutic effects include, but are not limited to, preventing disease occurrence or recurrence, alleviating symptoms, attenuating any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, improving or alleviating the disease state, and alleviating or improving prognosis.

[0067] The invention will be further described below in conjunction with specific examples. It should be understood that the specific embodiments described herein are presented by way of example and are not intended to limit the invention. The main features of the invention may be used in a variety of embodiments without departing from the scope of the invention.

[0068] Example 1

[0069] The process of suspension culture of spinal cord glioma cells: place the brain glioma tissue block (brain glioma tissue surgically removed in Tiantan Hospital according to the operation procedures in line with medical ethics) in a beaker, rinse it with Hanks solution three times to remove blood stains; then place it in a mixture containing penicillin and streptomycin for 60 minutes; use ophthalmic scissors to cut the tissue into 2-3 mm blocks for easy digestion; add trypsin solution equivalent to 50 times the volume of the total amount of tissue blocks, and then pour it into a conical flask, ligate the bottle mouth or plug it with a rubber stopper; place it in a 37°C incubator for digestion, and shake it every 20 minutes during the digestion process; the digestion time is 60 minutes; then filter out the tissue blocks that have not been fully digested through a suitable stainless steel sieve; centrifuge the digestion solution at 800 rpm to obtain sample cells, aspirate the supernatant, add primary culture medium to the precipitate, and add the primary culture medium to the precipitate until the cell density is 10 5 / mL, and then placed in a constant temperature incubator at 37°C for culture. The basic culture medium of the primary culture medium is a suspension culture medium, which includes: 20ng / mL EGF cytokine, 20ng / mL bFGF cytokine, 20ng / mL streptomycin and 20ng / mL penicillin, B27 (50×) and 20ng / mL transferrin.

[0070] The single cell suspension obtained by the above suspension culture was inoculated into an ultra-low adsorption culture dish for culture, and then digested into single cells with digestive enzymes. When the operation was repeated and subcultured to the fourth generation, some primary cells died, stopped growing or grew slowly, and another part of the primary cells were able to show a good proliferation state in the serum-free suspension culture medium. These cell lines showing a good proliferation state were selected as further screening objects, and MTT experiments and Transwell experiments were performed to detect the proliferation and migration abilities of the cell lines. The cell lines finally obtained included SCA-S10, SCA-S12, SCA-S41, SCA-S09, and SCA-S02. The gene mutations and copy number variations of spinal cord glioma cells were detected by whole exome sequencing. The results are as follows: Figure 1 As shown, it can be seen that different spinal glioma cells all have H3 K27M mutation (H3F3AK27M).

[0071] In this example, the spinal cord H3 K27M mutant cells derived from the above patients were divided into two groups: "high proliferation and replication pressure type" and "high immune infiltration type", among which SCA-S10 and SCA-S12 were "high immune infiltration type" tumor patient-derived cell models, and SCA-S41, SCA-S09, and SCA-S02 were "high proliferation and replication pressure type" cell models.

[0072] The sensitivity of Nedisertib (M3814) compound was evaluated using the above cell model. The specific process is as follows: spinal cord glioma cells in the logarithmic growth phase were taken, digested with trypsin, centrifuged to obtain cell pellets, resuspended in complete medium and counted, and the above spinal cord glioma cells were inoculated into 96-well cell culture plates at 5000 cells / well according to the counting results, and cultured in a 37°C incubator and 5% CO2 environment. After 24 hours, the cells were treated with drugs. The Nedisertib (M3814) compound was dissolved in DMSO to prepare a stock solution, and then diluted with complete medium to different drug concentrations. The gradient concentrations of the Nedisertib (M3814) compound were: 0, 0.04, 0.2, and 1.5 μM; the culture medium in the wells was removed, and the corresponding drug-containing solutions of each concentration were added, 100 μL per well. The well plate was returned to the incubator, and the cell proliferation was detected after 6 days. During the test, prepare the CCK8 working solution in advance, prepare the working solution of appropriate volume according to 100 μL serum-free culture medium and 10 μL CCK8 per well, and place it away from light. Take out the well plate from the incubator, remove the cell culture medium in the wells to be tested and add 110 μL CCK8 working solution respectively, continue to incubate for 2 hours, and then measure the absorbance at 450nm on the microplate reader, calculate the inhibition rate corresponding to each concentration, and use GraphPad7.0 software to calculate the IC50 value at the corresponding time point. The results are as follows: Figure 2 As shown, the "high immune infiltration type" SCA-S10 and SCA-S12 cells are relatively resistant to the treatment of Nedisertib (M3814) compound, while the "high proliferation and replication stress type" cells "SCA-S41, SCA-S09, SCA-S02" are relatively sensitive to the treatment of Nedisertib (M3814) compound.

[0073] Radiotherapy is currently the standard treatment for H3 K27 mutant spinal glioma. This example further evaluates whether the Nedisertib (M3814) compound combined with radiotherapy can effectively sensitize the effect of radiotherapy. The specific evaluation process includes: using 0, 2, 4, 6, 8Gy of radiotherapy doses to treat the above spinal glioma cells SCA-S41, SCA-S09, SCA-S02, SCA-S10 and SCA-S12, respectively, and administering Nedisertib (M3814) compound 0, 0.04, 0.2, 1.5 μmol, respectively, and measuring the number of surviving cells in different groups after 6 days of radiotherapy to evaluate their sensitivity to radiotherapy. The results are as follows: Figure 3 As shown, it can be intuitively seen that for H3 K27 mutant spinal cord glioma cells with high proliferation and replication stress, increasing the concentration of Nedisertib (M3814) compound can significantly sensitize the effect of radiotherapy.

[0074] Example 2

[0075] In this example, an orthotopic xenograft model was constructed by injecting luciferase-expressing spinal cord H3 K27M mutant tumor cells SCA09 into the spinal cord of nude mice, and the therapeutic effects of Nedisertib (M3814) compound alone and Nedisertib (M3814) compound combined with radiotherapy were measured. The specific measurement process is as follows:

[0076] SCA09 cells were injected into the spinal cord of nude mice, and the cells were allowed to grow in the spinal cord glioma for 14 days, which was set as day 0; the control group: normal saline was administered orally on days 0, 1, 2, 7, 8, 9, 14, 15 and 16, and simulated radiotherapy was given 4 hours after administration; the Nedisertib (M3814) group: Nedisertib (M3814) was administered orally on days 0, 1, 2, 7, 8, 9, 14, 15 and 16, and simulated radiotherapy was given 4 hours after administration Radiotherapy; Radiation group: normal saline was administered orally on days 0, 1, 2, 7, 8, 9, 14, 15 and 16, and 1 Gy of radiotherapy was given 4 hours after administration; Nedisertib (M3814) + radiation group: Nedisertib (M3814) was administered orally on days 0, 1, 2, 7, 8, 9, 14, 15 and 16, and 1 Gy of simulated radiotherapy was given 4 hours after administration; the size of cells in mice was shown by fluorescent in vivo imaging. Figure 4As shown, compared with the control group, both the Nedisertib (M3814) group and the radiotherapy group alone could effectively reduce the tumor volume at 28 days, while the Nedisertib (M3814) + radiotherapy group could more significantly reduce the tumor volume at 28 days.

[0077] This example further measured the tumor growth curve, such as Figure 5 As shown, it can also be seen from the tumor growth curve (change in average bioluminescence intensity) that the use of Nedisertib (M3814) or radiotherapy alone can inhibit the growth rate of tumors to a certain extent, while the use of Nedisertib (M3814) and radiotherapy together can more significantly inhibit the growth rate of mouse tumors.

[0078] In addition, compared with the control group, Nedisertib (M3814) or radiotherapy can prolong the survival of tumor-bearing mice to a certain extent, but the combination of Nedisertib (M3814) and radiotherapy can further prolong the survival of mice ( Figure 6 ).

[0079] These findings highlight the therapeutic value of Nedisertib (M3814) in spinal cord tumors, especially its value in sensitizing patients to radiotherapy.

[0080] Comparative Example

[0081] In this comparative example, the inhibitory effects of Nedisertib (M3814) and other commonly used compounds on the H3 K27M subtype of spinal cord glioma were further determined according to the determination method of Example 1. The drug concentration and effect are shown in FIG. Figure 7-8 , IC50 values ​​(μM) are shown in Table 1.

[0082] Table 1 The inhibitory effect of drugs on spinal cord glioma

[0083]

[0084] It can be seen that compared with other anti-tumor drugs, the Nedisertib (M3814) compound provided in the present application can effectively inhibit the growth of H3 K27M mutant spinal cord glioma, and can further sensitize radiotherapy, providing a new solution for the treatment of H3 K27M subtype spinal cord glioma.

[0085] The description of the above embodiments is only used to understand the method and core idea of ​​the present invention. It should be pointed out that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principle of the present invention, and these improvements and modifications will also fall within the scope of protection of the claims of the present invention.

Claims

1. Application of Nedisertib in the preparation of a pharmaceutical composition for treating spinal cord glioma; Preferably, the spinal cord glioma is a mutant spinal cord glioma; Preferably, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

2. The use of Nedisertib in the preparation of a pharmaceutical composition for sensitizing spinal cord glioma to radiotherapy; Preferably, the spinal cord glioma is a mutant spinal cord glioma; Preferably, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

3. The use according to claim 1 or 2, characterized in that: The pharmaceutical composition also includes other drugs / other radiosensitizers for treating spinal cord glioma.

4. The use according to claim 3, characterized in that: The other drugs for treating spinal cord glioma include methotrexate, cytarabine, palbociclib, temozolomide, and doxorubicin.

5. The use according to claim 3, characterized in that: The other radiosensitizers include metronidazole, misonidazole, nitroimidazole, benzamide, nicotinamide, cisplatin, mitomycin, tenizamine, nitrosoureas, and mercaptopurine.

6. The use according to claim 1 or 2, characterized in that: The pharmaceutical composition also includes pharmaceutically acceptable excipients.

7. The use according to claim 6, characterized in that: The pharmaceutically acceptable excipients include diluents, binders, surfactants, wetting agents, adsorption carriers, lubricants, fillers, and disintegrants.

8. The use according to claim 1 or 2, characterized in that: The dosage forms of the pharmaceutical composition include solutions, tablets, powders, suspensions, emulsions, granules, capsules, pills, inhalants, gels, suppositories, creams, jellies, and sprays.

9. A pharmaceutical composition for treating spinal cord glioma / radiotherapy sensitization of spinal cord glioma, characterized in that: The pharmaceutical composition includes Nedisertib; Preferably, the spinal cord glioma is a mutant spinal cord glioma; Preferably, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

10. A method for inhibiting the growth of spinal cord glioma cells in vitro, characterized in that: The method comprises administering Nedisertib; Preferably, the spinal cord glioma is a mutant spinal cord glioma; Preferably, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

Images