Review Article


DOI :10.26650/experimed.1573997   IUP :10.26650/experimed.1573997    Full Text (PDF)

Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions

Zeynep Birsu ÇinçinSoner Şahin

Bevacizumab is an important treatment for glioblastoma multiforme (GBM), especially after surgery, radiation, and chemotherapy, but it has not yet been successfully used to treat recurrent or progressive tumors. Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial growth factor A and inhibits neovascularization. Bevacizumab works by cutting off the blood supply to the tumor, thus alleviating symptoms and enhancing quality of life in situations where standard therapies have failed. Nonetheless, the effect of bevacizumab on the overall survival of patients with GBM was modest. Resistance ultimately occurs through the activation of alternative angiogenesis pathways or tumor evolution, including remodeling of the microenvironment and extracellular matrix. In response to these drawbacks, new strategies are under investigation, focusing on drug delivery systems based on nanotechnology. These include bevacizumab-loaded nanoparticles that cross the blood-brain barrier with greater efficiency, allowing for direct drug delivery to the tumor. Synergistic therapies using bevacizumab and classical chemotherapeutic agents or immunomodulatory therapies in these nanoparticle systems have shown promise in improving therapeutic potency by simultaneously targeting multiple tumor pathways or mechanisms, as demonstrated preclinically. Further development of these novel delivery approaches could lead to a more robust therapeutic paradigm for GBM, improving survival and quality of life for patients affected by this complex disease.


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References

  • 1. Lan Z, Li X, Zhang X. Glioblastoma: An update in pathology, molecular mechanisms and biomarkers. Int J Mol Sci 2024; 25(5): 3040. google scholar
  • 2. Bou-Gharios J, Noel G, Burckel H. Preclinical and clinical advances to overcome hypoxia in glioblastoma multiforme. Cell Death Dis 2024; 15(7): 503. google scholar
  • 3. Aghajani M, Jalilzadeh N, Aghebati-Maleki A, Yari A, Tabnak P, Mardi A, et al. Current approaches in glioblastoma multiforme immunotherapy. Clin Transl Oncol 2024; 26(7): 1584-612. google scholar
  • 4. Shahcheraghi SH, Alimardani M, Lotfi M, Uversky VN, Guetchueng ST, Palakurthi SS, et al. Advances in glioblastoma multiforme: Integrating therapy and pathology perspectives. Pathol Res Pract 2024; 257: 155285. google scholar
  • 5. Lorimer I. Modeling glioblastoma. eLife 2024; 13: e100824. google scholar
  • 6. Wu H, Guo C, Wang C, Xu J, Zheng S, Duan J, et al. Single-cell RNA sequencing reveals tumor heterogeneity, microenvironment, and drug-resistance mechanisms of recurrent glioblastoma. Cancer Sci 2023; 114(6): 2609-21. google scholar
  • 7. Tomar MS, Kumar A, Srivastava C, Shrivastava A. Elucidating the mechanisms of Temozolomide resistance in gliomas and the strategies to overcome the resistance. Biochim Biophys Acta Rev Cancer 2021; 1876(2): 188616. google scholar
  • 8. Cortes Ballen AI, Amosu M, Ravinder S, Chan J, Derin E, Slika H, et al. Metabolic reprogramming in glioblastoma multiforme: A review of pathways and therapeutic targets. Cells 2024; 13(18): 1574. google scholar
  • 9. Sarkar S, Patranabis S. Immunomodulatory signalling networks in glioblastoma multiforme: a comprehensive review of therapeutic approaches. Hum Cell 2024; 37(5): 1355-1377. google scholar
  • 10. Barzegar Behrooz A, Talaie Z, Jusheghani F, tos MJ, Klonisch T, Ghavami S. Wnt and PI3K/Akt/mTOR survival pathways as therapeutic targets in glioblastoma. Int J Mol Sci 2022; 23(3): 1353. google scholar
  • 11. Jena L, McErlean E, McCarthy H. Delivery across the blood-brain barrier: nanomedicine for glioblastoma multiforme. Drug Deliv Transl Res 2020; 10(2): 304-18. google scholar
  • 12. Song X, Qian H, Yu Y. Nanoparticles mediated the diagnosis and therapy of glioblastoma: bypass or cross the blood-brain barrier. Small 2023; 19(45): e2302613. google scholar
  • 13. Pearson JRD, Cuzzubbo S, McArthur S, Durrant LG, Adhikaree J, Tinsley CJ, et al. Immune escape in glioblastoma multiforme and the adaptation of immunotherapies for treatment. Front Immunol 2020; 11: 582106. google scholar
  • 14. Tang W, Fan W, Lau J, Deng L, Shen Z, Chen X. Emerging blood-brain-barrier-crossing nanotechnology for brain cancer theranostics. Chem Soc Rev 2019; 48(11): 2967-3014. google scholar
  • 15. Kılıç T, Yıldırım Ö, Şahin S, Pamir MN. Glial tümörlerin anjiogenezi. Turk Neurosurg 2005; 15(1): 1-9. google scholar
  • 16. Michaelsen SR, Staberg M, Pedersen H, Jensen KE, Majewski W, Broholm H, et al. VEGF-C sustains VEGFR2 activation under bevacizumab therapy and promotes glioblastoma maintenance. Neuro Oncol 2018; 20(11): 1462-74. google scholar
  • 17. Diaz RJ, Ali S, Qadir MG, De La Fuente MI, Ivan ME, Komotar RJ. The role of bevacizumab in the treatment of glioblastoma. J Neurooncol 2017; 133(3): 455-67. google scholar
  • 18. Arora H, Mammi M, Patel NM, Zyfi D, Dasari HR, Yunusa I, et al. Dexamethasone and overall survival and progression free survival in patients with newly diagnosed glioblastoma: a meta-analysis. J Neurooncol 2024; 166(1): 17-26. google scholar
  • 19. Pasupuleti V, Vora L, Prasad R, Nandakumar DN, Khatri DK. Glioblastoma preclinical models: strengths and weaknesses. Biochim Biophys Acta Rev Cancer 2024; 1879(1): 189059. google scholar
  • 20. Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, et al. Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma: The CheckMate 143 phase 3 randomized clinical trial. JAMA Oncol 2020; 6(7): 1003-10. google scholar
  • 21. Tsien CI, Pugh SL, Dicker AP, Raizer JJ, Matuszak MM, Lallana EC, et al. NRG Oncology/RTOG1205: A randomized phase II trial of concurrent bevacizumab and reirradiation versus bevacizumab alone as treatment for recurrent glioblastoma. J Clin Oncol 2023; 41(6): 1285-95. google scholar
  • 22. Tamura R, Tanaka T, Ohara K, Miyake K, Morimoto Y, Yamamoto Y, et al. Persistent restoration to the immunosupportive tumor microenvironment in glioblastoma by bevacizumab. Cancer Sci 2019; 110(2): 499-508. google scholar
  • 23. De Leo A, Ugolini A, Yu X, Scirocchi F, Scocozza D, Peixoto B, et al. Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma. Immunity 2024; 57(5): 1105-23.e8. google scholar
  • 24. Rashidi A, Billingham LK, Zolp A, Chia TY, Silvers C, Katz JL, et al. Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth. Cell Metab 2024; 36(1): 62-77.e8. google scholar
  • 25. Stadlbauer A, Roessler K, Zimmermann M, Buchfelder M, Kleindienst A, Doerfler A, et al. Predicting glioblastoma response to bevacizumab through MRI biomarkers of the tumor microenvironment. Mol Imaging Biol 2019; 21(4): 747-57. google scholar
  • 26. Fathi M, Razavi SM, Sojoodi M, Ahmadi A, Ebrahimi F, Namdar A, et al. Targeting the CTLA-4/B7 axes in glioblastoma: Preclinical evidence and clinical interventions. Expert Opin Ther Targets 2022; 26(11): 949-61. google scholar
  • 27. de Cristo Soares Alves A, Lavayen V, de Fraga Dias A, Bruinsmann FA, Scholl JN, Ce R, et al. EGFRvIII peptide nanocapsules and bevacizumab nanocapsules: A nose-to-brain multitarget approach against glioblastoma. Nanomedicine (Lond) 2021; 16(20): 1775-90. google scholar
  • 28. Cai Q, Li X, Xiong H, Fan H, Gao X, Vemireddy V, et al. Optical blood-brain-tumor barrier modulation expands therapeutic options for glioblastoma treatment. Nat Commun 2023; 14(1): 4934. google scholar
  • 29. Mauldin IS, Jo J, Wages NA, Yogendran LV, Mahmutovic A, Young SJ, et al. Proliferating CD8+ T cell infiltrates are associated with improved survival in glioblastoma. Cells 2021; 10(12): 3378. google scholar
  • 30. Jimenez-Pascual A, Mitchell K, Siebzehnrubl FA, Lathia JD. FGF2: A novel druggable target for glioblastoma? Expert Opin Ther Targets 2020; 24(4): 311-8. google scholar
  • 31. Singh RR, Mondal I, Janjua T, Popat A, Kulshreshtha R. Engineered smart materials for RNA based molecular therapy to treat glioblastoma. Bioact Mater 2023; 33: 396-423. google scholar
  • 32. Wiwatchaitawee K, Quarterman JC, Geary SM, Salem AK. Enhancement of therapies for glioblastoma (GBM) using nanoparticle-based delivery systems. AAPS PharmSciTech 2021; 22(2): 71. google scholar
  • 33. Ruiz-Garcia H, Ramirez-Loera C, Malouff TD, Seneviratne DS, Palmer JD, Trifiletti DM. Novel strategies for nanoparticle-based radiosensitization in glioblastoma. Int J Mol Sci 2021; 22(18): 9673. google scholar
  • 34. Lakshmi BA, Kim YJ. Modernistic and emerging developments of nanotechnology in glioblastoma-targeted theranostic applications. Int J Mol Sci 2022; 23(3): 1641. google scholar
  • 35. Jena L, McErlean E, McCarthy H. Delivery across the blood-brain barrier: Nanomedicine for glioblastoma multiforme. Drug Deliv Transl Res 2020; 10(2): 304-18. google scholar
  • 36. She L, Su L, Liu C. Bevacizumab combined with re-irradiation in recurrent glioblastoma. Front Oncol 2022; 12: 961014. google scholar
  • 37. Uddin MS, Mamun AA, Alghamdi BS, Tewari D, Jeandet P, Sarwar MS, et al. Epigenetics of glioblastoma multiforme: From molecular mechanisms to therapeutic approaches. Semin Cancer Biol 2022; 83: 100-20. google scholar
  • 38. Cui X, Huo D, Wang Q, Wang Y, Liu X, Zhao K, et al. RUNX1/NPM1/ H3K4me3 complex contributes to extracellular matrix remodeling via enhancing FOSL2 transcriptional activation in glioblastoma. Cell Death Dis 2024; 15(1): 98. google scholar
  • 39. Mahmoud AB, Ajina R, Aref S, Darwish M, Alsayb M, Taher M, et al. Advances in immunotherapy for glioblastoma multiforme. Front Immunol 2022; 13: 944452. google scholar
  • 40. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2023; 41(32): 4945-52. google scholar
  • 41. Collado J, Boland L, Ahrendsen JT, Miska J, Lee-Chang C. Understanding the glioblastoma tumor microenvironment: leveraging the extracellular matrix to increase immunotherapy efficacy. Front Immunol 2024; 15: 1336476. google scholar
  • 42. Chamarthy S, Mekala JR. Functional importance of glucose transporters and chromatin epigenetic factors in glioblastoma multiforme (GBM): possible therapeutics. Metab Brain Dis 2023; 38(5): 1441-69. google scholar
  • 43. Abdi F, Arkan E, Eidizadeh M, Valipour E, Naseriyeh T, Gamizgy YH, et al. The possibility of angiogenesis inhibition in cutaneous melanoma by bevacizumab-loaded lipid-chitosan nanoparticles. Drug Deliv Transl Res 2023; 13(2): 568-79. google scholar
  • 44. Khan MA, Kalsoom S, Ayub AR, Ilyas M, Hassan N, Irshad K, et al. Host-guest coupling to potentially increase the bio-accessibility of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea by nanocarrier graphyne for brain tumor therapy, a comprehensive quantum mechanics study. J Mol Graph Model 2023; 123: 108517. google scholar
  • 45. Tensaouti F, Desmoulin F, Gilhodes J, Roques M, Ken S, Lotterie JA, et al. Is pre-radiotherapy metabolic heterogeneity of glioblastoma predictive of progression-free survival? Radiother Oncol 2023; 183: 109665. google scholar
  • 46. Liang HT, Mizumoto M, Ishikawa E, Matsuda M, Tanaka K, Kohzuki H, et al. Peritumoral edema status of glioblastoma identifies patients reaching long-term disease control with specific progression patterns after tumor resection and high-dose proton boost. J Cancer Res Clin Oncol 2021; 147(12): 3503-16. google scholar
  • 47. Brown CE, Rodriguez A, Palmer J, Ostberg JR, Naranjo A, Wagner JR, et al. Off-the-shelf, steroid-resistant, IL13Ra2-specific CAR T cells for treatment of glioblastoma. Neuro Oncol 2022; 24(8): 1318-30. google scholar
  • 48. Jo J, Wen PY. Antiangiogenic therapy of high-grade gliomas. Prog Neurol Surg 2018; 31: 180-99. google scholar
  • 49. Kim MM, Umemura Y, Leung D. Bevacizumab and glioblastoma: Past, present, and future directions. Cancer J 2018; 24(4): 180-6. google scholar
  • 50. Carvalho B, Lopes JM, Silva R, Peixoto J, Leitâo D, Soares P, et al. The role of c-Met and VEGFR2 in glioblastoma resistance to bevacizumab. Sci Rep 2021; 11: 6067. google scholar

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APA

Çinçin, Z.B., & Şahin, S. (2024). Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions. Experimed, 14(3), 131-138. https://doi.org/10.26650/experimed.1573997


AMA

Çinçin Z B, Şahin S. Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions. Experimed. 2024;14(3):131-138. https://doi.org/10.26650/experimed.1573997


ABNT

Çinçin, Z.B.; Şahin, S. Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions. Experimed, [Publisher Location], v. 14, n. 3, p. 131-138, 2024.


Chicago: Author-Date Style

Çinçin, Zeynep Birsu, and Soner Şahin. 2024. “Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions.” Experimed 14, no. 3: 131-138. https://doi.org/10.26650/experimed.1573997


Chicago: Humanities Style

Çinçin, Zeynep Birsu, and Soner Şahin. Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions.” Experimed 14, no. 3 (Dec. 2024): 131-138. https://doi.org/10.26650/experimed.1573997


Harvard: Australian Style

Çinçin, ZB & Şahin, S 2024, 'Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions', Experimed, vol. 14, no. 3, pp. 131-138, viewed 21 Dec. 2024, https://doi.org/10.26650/experimed.1573997


Harvard: Author-Date Style

Çinçin, Z.B. and Şahin, S. (2024) ‘Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions’, Experimed, 14(3), pp. 131-138. https://doi.org/10.26650/experimed.1573997 (21 Dec. 2024).


MLA

Çinçin, Zeynep Birsu, and Soner Şahin. Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions.” Experimed, vol. 14, no. 3, 2024, pp. 131-138. [Database Container], https://doi.org/10.26650/experimed.1573997


Vancouver

Çinçin ZB, Şahin S. Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions. Experimed [Internet]. 21 Dec. 2024 [cited 21 Dec. 2024];14(3):131-138. Available from: https://doi.org/10.26650/experimed.1573997 doi: 10.26650/experimed.1573997


ISNAD

Çinçin, ZeynepBirsu - Şahin, Soner. Advanced Targeted Therapeutic Strategies for Glioblastoma Multiforme: Bevacizumab and Its Emerging Nanotechnology-Based Interventions”. Experimed 14/3 (Dec. 2024): 131-138. https://doi.org/10.26650/experimed.1573997



TIMELINE


Submitted26.10.2024
Accepted02.12.2024
Published Online11.12.2024

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