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Print ISSN: 2049-9450 Online ISSN: 2049-9469
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Review Open Access

Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review)

  • Authors:
    • Longfei Shao
    • Shuo Sun
    • Liling Yang
    • Jianmin Yang
    • Yinghao Gu
  • View Affiliations / Copyright

    Affiliations: School of Clinical Medicine Shandong Second Medical University, Weifang, Shandong 261053, P.R. China, Department of Neurosurgery, Zibo Central Hospital, Zibo, Shandong 255000, P.R. China
    Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 70
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    Published online on: October 13, 2026
       https://doi.org/10.3892/mco.2026.2979
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Abstract

The present study critically summarizes recent progress in therapeutic strategies and molecular mechanisms of glioblastoma (GBM) from 2020 to 2025, appraise the strength of evidence underlying emerging treatments, and provide practical references for individualized clinical decision‑making. Relevant studies were retrieved from PubMed, Embase and Web of Science using predefined search strings combining ‘glioblastoma’, ‘molecular classification’, ‘targeted therapy’, ‘immunotherapy’ and ‘drug resistance’. After duplicate removal and independent two‑reviewer screening, 86 studies were included and synthesized, and the evidence was graded according to study design (randomized trials vs. single‑arm early‑phase trials vs. preclinical studies). The results demonstrated that molecular classification centered on IDH mutation and MGMT promoter methylation has become the basis of GBM treatment decision‑making, although the WHO CNS5 classification now integrates additional diagnostic and prognostic biomarkers (for example, CDKN2A/B homozygous deletion, EGFR amplification, TERT promoter mutation, chromosome 7 gain/10 loss). 5‑aminolevulinic acid fluorescence‑guided surgery improves the extent of resection, and tumor treating fields provide an additional survival benefit in newly diagnosed GBM. Emerging approaches, including dual‑target CAR‑T cells, mRNA vaccines and metabolic inhibitors, have shown preliminary signals of activity in recurrent GBM, but most remain investigational and are supported by early‑phase trials with small sample sizes. GBM treatment resistance arises from interconnected DNA repair, epigenetic, metabolic, tumor microenvironment and glioblastoma stem cell networks. In conclusion, GBM management is transitioning from empirical therapy toward molecularly guided precision therapy, but the translational gap between promising preclinical findings and proven clinical benefit remains substantial. Multimodal strategies integrating refined molecular classification, blood‑brain barrier‑penetrant drug delivery and rationally combined, rigorously tested therapies represent the most realistic path to improving GBM outcomes.
View Figures

Figure 1

Interconnected network of
glioblastoma therapy resistance mechanisms. DNA repair, epigenetic
reprogramming, metabolic reprogramming, tumor microenvironment
immunosuppression and GSC stemness are mutually reinforcing; orange
arrows indicate crosstalk. miR, microRNA; HIF-1α, hypoxia-inducible
factor 1α; TMZ, temozolomide; ECM, extracellular matrix; GLS,
glutaminase; FASN, fatty acid synthase; miR, microRNA; TAMs,
tumor-associated macrophages; MMP9, matrix metalloproteinase 9;
ROS, reactive oxygen species; GSCs, glioblastoma stem cell.

Figure 2

PRISMA-style literature selection
flowchart. The 772 records excluded at title/abstract screening
comprised 360 non-GBM/out-of-scope records, 162 case reports, 98
conference abstracts or gray-literature items, 68 non-English
records and 84 records with incomplete or unclear data. The 128
records excluded at full-text assessment comprised 47 with
incomplete data, 36 with low methodological quality, 20 with
unclear conclusions, 14 case reports/conference abstracts and 11
non-GBM glioma subtypes. GBM, glioblastoma.
View References

1 

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, et al: The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro Oncol. 23:1231–1251. 2021.PubMed/NCBI View Article : Google Scholar

2 

van den Bent MJ, Geurts M, French PJ, Smits M, Capper D, Bromberg JEC and Chang SM: Primary brain tumours in adults. Lancet. 402:1564–1579. 2023.PubMed/NCBI View Article : Google Scholar

3 

Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS and Khasraw M: Management of glioblastoma: State of the art and future directions. CA Cancer J Clin. 70:299–312. 2020.PubMed/NCBI View Article : Google Scholar

4 

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005.PubMed/NCBI View Article : Google Scholar

5 

Qazi MA, Vora P, Venugopal C, Sidhu SS, Moffat J, Swanton C and Singh SK: Intratumoral heterogeneity: Pathways to treatment resistance and relapse in human glioblastoma. Ann Oncol. 28:1448–1456. 2017.PubMed/NCBI View Article : Google Scholar

6 

Weller M, Wen PY, Chang SM, Dirven L, Lim M, Monje M and Reifenberger G: Glioma. Nat Rev Dis Primers. 10(33)2024.PubMed/NCBI View Article : Google Scholar

7 

Neftel C, Laffy J, Filbin MG, Hara T, Shore ME, Rahme GJ, Richman AR, Silverbush D, Shaw ML, Hebert CM, et al: An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell. 178(849.e21)2019.PubMed/NCBI View Article : Google Scholar

8 

McMahon JT, Studer M, Ulrich B, Revuelta Barbero JM, Pradilla I, Palacios-Ariza MA and Pradilla G: Circulating tumor DNA in adults with glioma: A systematic review and Meta-analysis of biomarker performance. Neurosurgery. 91:231–238. 2022.PubMed/NCBI View Article : Google Scholar

9 

Horbinski C, Solomon DA, Lukas RV, Packer RJ, Brastianos P, Wen PY, Snuderl M, Berger MS, Chang S, Fouladi M, et al: Molecular testing for the world health organization classification of central nervous system tumors: A review. JAMA Oncol. 11:317–328. 2025.PubMed/NCBI View Article : Google Scholar

10 

Wen PY and Packer RJ: The 2021 WHO classification of tumors of the central nervous system: Clinical implications. Neuro Oncol. 23:1215–1217. 2021.PubMed/NCBI View Article : Google Scholar

11 

Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, et al: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 352:997–1003. 2005.PubMed/NCBI View Article : Google Scholar

12 

Barault L, Amatu A, Bleeker FE, Moutinho C, Falcomatà C, Fiano V, Cassingena A, Siravegna G, Milione M, Cassoni P, et al: Digital PCR quantification of MGMT methylation refines prediction of clinical benefit from alkylating agents in glioblastoma and metastatic colorectal cancer. Ann Oncol. 26:1994–1999. 2015.PubMed/NCBI View Article : Google Scholar

13 

Reardon DA and Cahill DP: A new era for glioma therapy-targeting mutant IDH. Nat Rev Clin Oncol. 20:737–738. 2023.PubMed/NCBI View Article : Google Scholar

14 

Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, Mendez J, Yust-Katz S, Welsh L, Mason WP, et al: Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 389:589–601. 2023.PubMed/NCBI View Article : Google Scholar

15 

Mukherjee I, Park J, Patel AP and Baliga NS: Transcriptional mechanisms of phenotypic plasticity in glioblastoma. J Clin Oncol. 42 (16_suppl)(e14027)2024.

16 

LeBlanc VG, Trinh DL, Aslanpour S, Hughes M, Livingstone D, Jin D, Ahn BY, Blough MD, Cairncross JG, Chan JA, et al: Single-cell landscapes of primary glioblastomas and matched explants and cell lines show variable retention of inter- and intratumor heterogeneity. Cancer Cell. 40:79–392.e9. 2022.PubMed/NCBI View Article : Google Scholar

17 

Migliozzi S, Adabbo B, Garofano L, Wu F, Davila P, Komotar RJ, Ivan ME, Shah AH, Currall BB, Williams S, et al: Restraint of cancer cell plasticity by spatial homotypic clustering. Cancer Cell. 43:2206–2223.e10. 2025.PubMed/NCBI View Article : Google Scholar

18 

Hamed AA, Hua K, Trinh QM, Simons BD, Marioni JC, Stein LD and Dirks PB: Gliomagenesis mimics an injury response orchestrated by neural crest-like cells. Nature. 638:499–509. 2025.PubMed/NCBI View Article : Google Scholar

19 

Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F and Reulen HJ: ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol. 7:392–401. 2006.PubMed/NCBI View Article : Google Scholar

20 

Moiyadi A, Syed P and Srivastava S: Fluorescence-guided surgery of malignant gliomas based on 5-aminolevulinic acid: Paradigm shifts but not a panacea. Nat Rev Cancer. 14(146)2014.PubMed/NCBI View Article : Google Scholar

21 

McCracken DJ, Schupper AJ, Lakomkin N, Malcolm J, Painton Bray D and Hadjipanayis CG: Turning on the light for brain tumor surgery: A 5-aminolevulinic acid story. Neuro Oncol. 24 (Suppl 6):S52–S61. 2022.PubMed/NCBI View Article : Google Scholar

22 

Coty-Fattal Z, Smith H, McCord M, Mejia-Bautista M, Dittman D, Primdahl D, Conway K, Becker N, Ahrendsen JT, Santana-Santos L, et al: Rapid assessment of MGMT promoter methylation status by droplet digital polymerase chain reaction on intraoperative smear preparation: A proof-of-concept study. J Neuropathol Exp Neurol. 85:280–284. 2025.PubMed/NCBI View Article : Google Scholar

23 

Singh S, Dey D, Barik D, Mohapatra I, Kim S, Sharma M, Prasad S, Wang P, Singh A and Singh G: Glioblastoma at the crossroads: Current understanding and future therapeutic horizons. Signal Transduct Target Ther. 10(213)2025.PubMed/NCBI View Article : Google Scholar

24 

Arienti C, Pignatta S, Zanoni M, Zamagni A, Cortesi M, Sarnelli A, Romeo A, Arpa D, Longobardi P, Bartolini D, et al: High-pressure oxygen rewires glucose metabolism of patient-derived glioblastoma cells and fuels inflammasome response. Cancer Lett. 506:152–166. 2021.PubMed/NCBI View Article : Google Scholar

25 

Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, et al: Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: A randomized clinical trial. JAMA. 318:2306–2316. 2017.PubMed/NCBI View Article : Google Scholar

26 

Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bähr O, et al: Effect of Nivolumab vs bevacizumab in patients with recurrent glioblastoma: The CheckMate 143 phase 3 randomized clinical trial. JAMA Oncol. 6:1003–1010. 2020.PubMed/NCBI View Article : Google Scholar

27 

Schalper KA, Rodriguez-Ruiz ME, Diez-Valle R, López-Janeiro A, Porciuncula A, Idoate MA, Inogés S, de Andrea C, López-Diaz de Cerio A, Tejada S, et al: Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Nat Med. 25:470–476. 2019.PubMed/NCBI View Article : Google Scholar

28 

Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L, Chu T, Bordbar D, Shan D, Samanamud J, Mahajan A, et al: Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. Nat Med. 25:462–469. 2019.PubMed/NCBI View Article : Google Scholar

29 

Kreatsoulas D, Bolyard C, Wu BX, Cam H, Giglio P and Li Z: Translational landscape of glioblastoma immunotherapy for physicians: Guiding clinical practice with basic scientific evidence. J Hematol Oncol. 15(80)2022.PubMed/NCBI View Article : Google Scholar

30 

Zhang Y, Chi X, Feng R, Xian N, Huang N, Sun S, Zhao X, Zhang P, Liu K, Ma Y, et al: Intracranial delivery of B7-H3-targeting CAR-T cells for recurrent glioblastoma: A phase 1 trial. Nat Med. 32:3268–3275. 2026.PubMed/NCBI View Article : Google Scholar

31 

Clubb JD, Shih RM, Gao TA, Shafer A, Vajragiri S, Lam K, Talluri S, Bouren A, Brown CE, Ruivo P, et al: Armored chimeric antigen receptor T-cell therapy targets antigen-heterogeneous glioma. Cancer Res. 86:3781–3800. 2026.PubMed/NCBI View Article : Google Scholar

32 

Kong S, Sengupta S, Tyler B, Bais AJ, Ma Q, Doucette S, Zhou J, Sahin A, Carter BS, Brem H, et al: Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells. Clin Cancer Res. 18:5949–5960. 2012.PubMed/NCBI View Article : Google Scholar

33 

Mitchell DA, Batich KA, Gunn MD, Huang MN, Sanchez-Perez L, Nair SK, Congdon KL, Reap EA, Archer GE, Desjardins A, et al: Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 519:366–369. 2015.PubMed/NCBI View Article : Google Scholar

34 

Berneman ZN, De Laere M, Germonpré P, Huizing MT, Willemen Y, Lion E, De Reu H, Van den Bossche J, Van den Brande J, Specenier P, et al: WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: Type 1 T-lymphocyte responses are associated with clinical outcome. J Hematol Oncol. 18(9)2025.PubMed/NCBI View Article : Google Scholar

35 

Garfinkle EAR, Perales-Linares R, Gimple RC, Livingstone AJ, Roberts KF, Butt OH, Goedegebuure SP, McLellan MD, Chang GS, Hundal J, et al: Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: A phase 1 trial. Nature Cancer. 7:1064–1079. 2026.PubMed/NCBI View Article : Google Scholar

36 

Van Den Bent MJ, French P, Eoli M, Sepúlveda JM, Walenkamp AME, Frenel JS, Franceschi E, Clement PM, Weller M, de Heer I, et al: Updated results of the INTELLANCE 2/EORTC trial 1410 randomized phase II study on Depatux-M alone, Depatux-M in combination with temozolomide (TMZ) and either TMZ or lomustine (LOM) in recurrent EGFR amplified glioblastoma (NCT02343406). J Clin Oncol: Jun 1, 2018 (Epub ahead of print). doi: 10.1200/JCO.2018.36.15_suppl.202.

37 

Padovan M, Eoli M, Pellerino A, Rizzato S, Caserta C, Simonelli M, Michiara M, Caccese M, Anghileri E, Cerretti G, et al: Depatuxizumab mafodotin (Depatux-M) plus temozolomide in recurrent glioblastoma patients: Real-world experience from a multicenter study of italian association of Neuro-oncology (AINO). Cancers (Basel). 13(2773)2020.PubMed/NCBI View Article : Google Scholar

38 

Mair MJ, Bartsch R, Le Rhun E, Berghoff AS, Brastianos PK, Cortes J, Gan HK, Lin NU, Lassman AB, Wen PY, et al: Understanding the activity of antibody-drug conjugates in primary and secondary brain tumours. Nat Rev Clin Oncol. 20:372–389. 2023.PubMed/NCBI View Article : Google Scholar

39 

Gan HK, van den Bent M, Lassman AB, Reardon DA and Scott AM: Antibody-drug conjugates in glioblastoma therapy: The right drugs to the right cells. Nat Rev Clin Oncol. 14:695–707. 2017.PubMed/NCBI View Article : Google Scholar

40 

Furnari FB, Cloughesy TF, Cavenee WK and Mischel PS: Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma. Nat Rev Cancer. 15:302–310. 2015.PubMed/NCBI View Article : Google Scholar

41 

Todo T, Ito H, Ino Y, Ohtsu H, Ota Y, Shibahara J and Tanaka M: Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: A phase 2 trial. Nat Med. 28:1630–1639. 2022.PubMed/NCBI View Article : Google Scholar

42 

Nassiri F, Patil V, Yefet LS, Singh O, Liu J, Dang RMA, Yamaguchi TN, Daras M, Cloughesy TF, Colman H, et al: Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: A phase 1/2 trial. Nat Med. 29:1370–1378. 2023.PubMed/NCBI View Article : Google Scholar

43 

Desjardins A, Gromeier M, Herndon JE II, Beaubier N, Bolognesi DP, Friedman AH, Friedman HS, McSherry F, Muscat AM, Nair S, et al: Recurrent Glioblastoma treated with recombinant poliovirus. N Engl J Med. 379:150–161. 2018.PubMed/NCBI View Article : Google Scholar

44 

Suvà ML, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle JC, Baumer K, Le Bitoux MA, Marino D, Cironi L, et al: EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res. 69:9211–9218. 2009.PubMed/NCBI View Article : Google Scholar

45 

Jin X, Kim LJY, Wu Q, Wallace LC, Prager BC, Sanvoranart T, Gimple RC, Wang X, Mack SC, Miller TE, et al: Targeting glioma stem cells through combined BMI1 and EZH2 inhibition. Nat Med. 23:1352–1361. 2017.PubMed/NCBI View Article : Google Scholar

46 

Stefan D, Lesueur P, Lequesne J, Feuvret L, Bronnimann C, Castéra M, Brachet PE, Hrab I, Ducloie M, Lacroix J, et al: Olaparib, temozolomide and concomitant radiotherapy for partially or biopsy-only glioblastoma first-line treatment: Results from the OLA-TMZ-RTE-01 phase 1 study. Clin Cancer Res. 31:1212–1222. 2025.PubMed/NCBI View Article : Google Scholar

47 

Natsume A, Ito M, Katsushima K, Ohka F, Hatanaka A, Shinjo K, Sato S, Takahashi S, Ishikawa Y, Takeuchi I, et al: Chromatin regulator PRC2 is a key regulator of epigenetic plasticity in glioblastoma. Cancer Res. 73:4559–4570. 2013.PubMed/NCBI View Article : Google Scholar

48 

Minami JK, Morrow D, Bayley NA, Fernandez EG, Salinas JJ, Tse C, Zhu H, Su B, Plawat R, Jones A, et al: CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis. Cancer Cell. 41:1048–1060.e9. 2023.PubMed/NCBI View Article : Google Scholar

49 

Duman C, Yaqubi K, Hoffmann A, Acikgöz AA, Korshunov A, Bendszus M, Herold-Mende C, Liu HK and Alfonso J: Acyl-CoA-binding protein drives glioblastoma tumorigenesis by sustaining fatty acid oxidation. Cell Metab. 30:274–289.e5. 2019.PubMed/NCBI View Article : Google Scholar

50 

Masui K, Tanaka K, Akhavan D, Babic I, Gini B, Matsutani T, Iwanami A, Liu F, Villa GR, Gu Y, et al: mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc. Cell Metab. 18:726–739. 2013.PubMed/NCBI View Article : Google Scholar

51 

Ye Z, Ai X, Yang K, Yang Z, Fei F, Liao X, Qiu Z, Gimple RC, Yuan H, Huang H, et al: Targeting microglial metabolic rewiring synergizes with immune-checkpoint blockade therapy for glioblastoma. Cancer Discov. 13:974–1001. 2023.PubMed/NCBI View Article : Google Scholar

52 

Waibl Polania J, Hoyt-Miggelbrink A, Tomaszewski WH, Wachsmuth LP, Lorrey SJ, Wilkinson DS, Lerner E, Woroniecka K, Finlay JB, Ayasoufi K and Fecci PE: Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion. Immunity. 58:232–246.e6. 2025.PubMed/NCBI View Article : Google Scholar

53 

Wang W, Li T, Cheng Y, Li F, Qi S, Mao M, Wu J, Liu Q, Zhang X, Li X, et al: Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization. Cancer Cell. 42:815–832.e12. 2024.PubMed/NCBI View Article : Google Scholar

54 

Sattiraju A, Kang S, Giotti B, Chen Z, Marallano VJ, Brusco C, Ramakrishnan A, Shen L, Tsankov AM, Hambardzumyan D, et al: Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression. Immunity. 56:1825–1843.e6. 2023.PubMed/NCBI View Article : Google Scholar

55 

Jeon HM, Kim JY, Cho HJ, Lee WJ, Nguyen D, Kim SS, Oh YT, Kim HJ, Jung CW, Pinero G, et al: Tissue factor is a critical regulator of radiation therapy-induced glioblastoma remodeling. Cancer Cell. 41:1480–1497.e9. 2023.PubMed/NCBI View Article : Google Scholar

56 

Hoogstrate Y, Draaisma K, Ghisai SA, van Hijfte L, Barin N, de Heer I, Coppieters W, van den Bosch TPP, Bolleboom A, Gao Z, et al: Transcriptome analysis reveals tumor microenvironment changes in glioblastoma. Cancer Cell. 41:678–692.e7. 2023.PubMed/NCBI View Article : Google Scholar

57 

Man J, Yu X, Huang H, Zhou W, Xiang C, Huang H, Miele L, Liu Z, Bebek G, Bao S and Yu JS: Hypoxic induction of vasorin regulates Notch1 turnover to maintain glioma Stem-like cells. Cell Stem Cell. 22:104–118.e6. 2018.PubMed/NCBI View Article : Google Scholar

58 

Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE, et al: Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell. 15:501–513. 2009.PubMed/NCBI View Article : Google Scholar

59 

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD and Rich JN: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444:756–760. 2006.PubMed/NCBI View Article : Google Scholar

60 

Wu Y, Song Y, Wang R and Wang T: Molecular mechanisms of tumor resistance to radiotherapy. Mol Cancer. 22(96)2023.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Shao L, Sun S, Yang L, Yang J and Gu Y: Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review). Mol Clin Oncol 25: 70, 2026.
APA
Shao, L., Sun, S., Yang, L., Yang, J., & Gu, Y. (2026). Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review). Molecular and Clinical Oncology, 25, 70. https://doi.org/10.3892/mco.2026.2979
MLA
Shao, L., Sun, S., Yang, L., Yang, J., Gu, Y."Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review)". Molecular and Clinical Oncology 25.5 (2026): 70.
Chicago
Shao, L., Sun, S., Yang, L., Yang, J., Gu, Y."Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review)". Molecular and Clinical Oncology 25, no. 5 (2026): 70. https://doi.org/10.3892/mco.2026.2979
Copy and paste a formatted citation
x
Spandidos Publications style
Shao L, Sun S, Yang L, Yang J and Gu Y: Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review). Mol Clin Oncol 25: 70, 2026.
APA
Shao, L., Sun, S., Yang, L., Yang, J., & Gu, Y. (2026). Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review). Molecular and Clinical Oncology, 25, 70. https://doi.org/10.3892/mco.2026.2979
MLA
Shao, L., Sun, S., Yang, L., Yang, J., Gu, Y."Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review)". Molecular and Clinical Oncology 25.5 (2026): 70.
Chicago
Shao, L., Sun, S., Yang, L., Yang, J., Gu, Y."Frontier therapeutic strategies and molecular mechanisms of glioblastoma (Review)". Molecular and Clinical Oncology 25, no. 5 (2026): 70. https://doi.org/10.3892/mco.2026.2979
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