AccScience Publishing / MI / Online First / DOI: 10.36922/mi.5075
Submit to MI
Cite this article
6
Download
120
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
MINI-REVIEW

Navigating glioblastoma therapy: A narrative review of emerging immunotherapeutics and small-molecule inhibitors

Matthew A. Abikenari1* ,  Iman Enayati2 ,  Daniel M. Fountain1,3 ,  Maria Isabel Leite1
Show Less
1 Nuffield Department of Clinical Neurosciences, University of Oxford and Oxford University Hospitals, NHS Foundation Trust, Oxford, United Kingdom
2 UCLA Department of Orthopaedic Surgery, University of California, Los Angeles, California, United States of America
3 Department of Medicine, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
MI, 5075 https://doi.org/10.36922/mi.5075
Submitted: 8 October 2024 | Revised: 22 November 2024 | Accepted: 9 December 2024 | Published: 30 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Glioblastoma multiforme (GBM) is the most common malignant primary tumor of the central nervous system (CNS), accounting for the majority of brain tissue tumors and CNS neoplasms. GBM has an incidence rate of 3.2/100,000 people in the United States, with an abysmal survival rate of 15 months with treatment and under 3 months for untreated patients. GBM remains incurable, with no disease-modifying treatment available. As a grade IV astrocytoma, GBM is highly aggressive, characterized by rapid proliferation, high metabolic demands, substantial angiogenesis, and diffuse infiltration of healthy parenchyma. The GBM genome is highly heterogeneous, with unpredictable amplification patterns, dysregulation, and mutational activation of receptor tyrosine kinase genes, tumor suppressor genes, and growth factor signaling. GBM’s indistinct tumor margins, its highly adaptive interaction with the brain microenvironment, and the existence of the blood-brain barrier and the blood-brain tumor barrier further limit effective anti-GBM therapeutic strategies. Hence, anti-GBM drug discoveries and molecular techniques that aim for patient-specific treatment stratification are of profound clinical and therapeutic significance. The current paper aims to outline the fundamental pathophysiology, tumorigenicity, and immunosuppressive mechanism of GBMs, review current treatment options for GBMs, and examine the contemporary challenges and advances in anti-GBM drug discovery and delivery. Finally, the paper aims to shed light on the emergence of small-molecule inhibitors, immune checkpoint inhibitors, and vaccination therapy as potentially efficacious therapeutic strategies for treating GBM.

Keywords
Glioblastoma multiforme
Immunotherapy
Checkpoint inhibitors
Anti-GBM therapeutic strategies
Immunosuppressive mechanism
Small-molecule inhibitors
Funding
None.
Conflict of interest
The authors declare that they have no competing interest.
References
  1. Omuro A. Glioblastoma and other malignant gliomas: A clinical review. JAMA. 2013;310(17):1842. doi: 10.1001/jama.2013.280319

 

  1. Thakkar JP, Dolecek TA, Horbinski C, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev. 2014;23(10):1985-1996. doi: 10.1158/1055-9965.epi-14-0275

 

  1. Tamimi AF, Juweid M. Epidemiology and outcome of glioblastoma. In: Glioblastoma. Brisbane, AU: Codon Publications; 2017. p. 143-153. doi: 10.15586/codon.glioblastoma.2017.ch8

 

  1. Ostrom QT, Gittleman H, Fulop J, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro Oncol. 2015;17(suppl 4):iv1-iv62. doi: 10.1093/neuonc/nov189

 

  1. Koshy M, Villano JL, Dolecek TA, et al. Improved survival time trends for glioblastoma using the seer 17 population-based registries. J Neurooncol. 2011;107(1):207-212. doi: 10.1007/s11060-011-0738-7

 

  1. Malmström A, Grønberg BH, Marosi C, et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: The nordic randomised, phase 3 trial. Lancet Oncol. 2012;13(9):916-926. doi: 10.1016/s1470-2045(12)70265-6

 

  1. Zhang H, Wang R, Yu Y, Liu J, Luo T, Fan F. Glioblastoma treatment modalities besides surgery. J Cancer. 2019;10(20):4793-4806. doi: 10.7150/jca.32475

 

  1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 2016;131(6):803-820. doi: 10.1007/s00401-016-1545-1

 

  1. Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013;19(4):764-772. doi: 10.1158/1078-0432.ccr-12-3002

 

  1. Kleihues P, Ohgaki H. Primary and secondary glioblastomas: From concept to clinical diagnosis. Neuro Oncol. 1999;1(1):44-51. doi: 10.1093/neuonc/1.1.44

 

  1. Nobusawa S, Watanabe T, Kleihues P, Ohgaki H. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res. 2009;15(19): 6002-6007. doi: 10.1158/1078-0432.ccr-09-0715

 

  1. Amankulor NM, Kim Y, Arora S, et al. Mutant IDH1 regulates the tumor-associated immune system in gliomas. Genes Dev. 2017;31(8):774-786. doi: 10.1101/gad.294991.116

 

  1. Waitkus MS, Yan H. Targeting isocitrate dehydrogenase mutations in cancer: Emerging evidence and diverging strategies. Clin Cancer Res. 2021;27(2):383-388. doi: 10.1158/1078-0432.ccr-20-1827

 

  1. Nakada M, Kita D, Watanabe T, et al. Aberrant signaling pathways in glioma. Cancers (Basel). 2011;3(3):3242-3278. doi: 10.3390/cancers3033242

 

  1. McLendon R, Friedman A, Bigner D. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216):1061-1068. doi: 10.1038/nature07385

 

  1. Nagane M. Neuro-oncology: Continuing multidisciplinary progress. Lancet Neurol. 2011;10(1):18-20. doi: 10.1016/s1474-4422(10)70302-1

 

  1. Stupp R, Weller M. 2010: Neuro-oncology is moving! Curr Opin Neurol. 2010;23(6):553-555. doi: 10.1097/wco.0b013e3283407eed

 

  1. Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: The avenue to a cure for malignant glioma. CA Cancer J Clin. 2010;60(3):166-193. doi: 10.3322/caac.20069

 

  1. Brandao M, Simon T, Critchley G, Giamas G. Astrocytes, the rising stars of the glioblastoma microenvironment. Glia. 2018;67(5):779-790. doi: 10.1002/glia.23520

 

  1. Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes Dev. 2007;21(21):2683-2710. doi: 10.1101/gad.1596707

 

  1. Farin A, Suzuki SO, Weiker M, Goldman JE, Bruce JN, Canoll P. Transplanted glioma cells migrate and proliferate on host brain vasculature: A dynamic analysis. Glia. 2006;53(8):799-808. doi: 10.1002/glia.20334

 

  1. De Gooijer MC, Guillén Navarro M, Bernards R, Wurdinger T, van Tellingen O. An experimenter’s guide to glioblastoma invasion pathways. Trends Mol Med. 2018;24(9):763-780. doi: 10.1016/j.molmed.2018.07.003

 

  1. Coniglio SJ, Eugenin E, Dobrenis K, et al. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med. 2012;18(3):519-527. doi: 10.2119/molmed.2011.00217

 

  1. Xie Q, Mittal S, Berens ME. Targeting adaptive glioblastoma: An overview of proliferation and invasion. Neuro Oncol. 2014;16(12):1575-1584. doi: 10.1093/neuonc/nou147

 

  1. Mrugala MM. Advances and challenges in the treatment of glioblastoma: A clinician’s perspective. Discov Med. 2013;15(83):221-230.

 

  1. Ohka F, Natsume A, Wakabayashi T. Current trends in targeted therapies for glioblastoma multiforme. Neurol Res Int. 2012;2012:878425. doi: 10.1155/2012/878425

 

  1. Scott J, Tsai YY, Chinnaiyan P, Yu HHM. Effectiveness of radiotherapy for elderly patients with glioblastoma. Int J Radiat Oncol Biol Phys. 2011;81(1):206-210. doi: 10.1016/j.ijrobp.2010.04.033

 

  1. Nabors LB, Portnow J, Ammirati M, et al. Central nervous system cancers, version 1.2015. J Natl Compr Canc Netw. 2015;13(10):1191-1202. doi: 10.6004/jnccn.2015.0148

 

  1. Bronte G, Rolfo C, Giovannetti E, et al. Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects. Crit Rev Oncol Hematol. 2014;89(2):300-313. doi: 10.1016/j.critrevonc.2013.08.003

 

  1. Iacob G, Dinca EB. Current data and strategy in glioblastoma multiforme. J Med Life. 2009;2(4):386-393.

 

  1. Fabian D, Guillermo Prieto Eibl MP, Alnahhas I, et al. Treatment of glioblastoma (GBM) with the addition of tumor-treating fields (TTF): A review. Cancers (Basel). 2019;11(2):174. doi: 10.3390/cancers11020174

 

  1. Stupp R, Taillibert S, Kanner AA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: A randomized clinical trial. JAMA. 2015;314(23):2535. doi: 10.1001/jama.2015.16669

 

  1. Canessa A, Del Bono V, Miletich F, Pistoia V. Serum cytokines in toxoplasmosis: Increased levels of interferon-gamma in immunocompetent patients with lymphadenopathy but not in AIDS patients with encephalitis. J Infect Dis. 1992;165(6):1168-1170. doi: 10.1093/infdis/165.6.1168

 

  1. Waksman BH, Adams RD. Allergic neuritis: An experimental disease of rabbits induced by the injection of peripheral nervous tissue and adjuvants. J Exp Med. 1955;102(2):213-236. doi: 10.1084/jem.102.2.213

 

  1. Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337-341. doi: 10.1038/nature14432

 

  1. Chae M, Peterson TE, Balgeman A, et al. Increasing glioma-associated monocytes leads to increased intratumoral and systemic myeloid-derived suppressor cells in a murine model. Neuro Oncol. 2014;17(7):978-991. doi: 10.1093/neuonc/nou343

 

  1. Nduom EK, Weller M, Heimberger AB. Immunosuppressive mechanisms in glioblastoma. Neuro Oncol. 2015;17(suppl 7): vii9-vii14. doi: 10.1093/neuonc/nov151

 

  1. Roszman T, Elliott L, Brooks W. Modulation of T-cell function by gliomas. Immunol Today. 1991;12(10):370-374. doi: 10.1016/0167-5699(91)90068-5

 

  1. Bodmer S, Strommer K, Frei K, et al. Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2. J Immunol. 1989;143(10):3222-3229.

 

  1. Huettner C, Czub S, Kerkau S, Roggendorf W, Tonn JC. Interleukin 10 is expressed in human gliomas in vivo and increases glioma cell proliferation and motility in vitro. Anticancer Res. 1997;17(5A):3217-3224.

 

  1. Huettner C, Paulus W, Roggendorf W. Messenger RNA expression of the immunosuppressive cytokine IL-10 in human gliomas. Am J Pathol. 1995;146(2):317-322.

 

  1. Jackson CM, Kochel CM, Nirschl CJ, et al. Systemic tolerance mediated by melanoma brain tumors is reversible by radiotherapy and vaccination. Clin Cancer Res. 2016;22(5):1161-1172. doi: 10.1158/1078-0432.ccr-15-1516

 

  1. Lauro GM, Di Lorenzo N, Grossi M, Maleci A, Guidetti B. Prostaglandin E2 as an immunomodulating factor released in vitro by human glioma cells. Acta Neuropathol. 1986;69(3-4): 278-282. doi: 10.1007/bf00688305

 

  1. Wiendl H, Mitsdoerffer M, Hofmeister V, et al. A functional role of HLA-G expression in human gliomas: An alternative strategy of immune escape. J Immunol. 2002;168(9):4772-4780. doi: 10.4049/jimmunol.168.9.4772

 

  1. Wischhusen J, Friese MA, Mittelbronn M, Meyermann R, Weller M. HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: Implications for immune escape in vivo. J Neuropathol Exp Neurol. 2005;64(6):523-528. doi: 10.1093/jnen/64.6.523

 

  1. Parney IF, Waldron JS, Parsa AT. Flow cytometry and in vitro analysis of human glioma-associated macrophages. Laboratory investigation. J Neurosurg. 2009;110(3):572-582. doi: 10.3171/2008.7.jns08475

 

  1. Preusser M, Lim M, Hafler DA, Reardon DA, Sampson JH. Prospects of immune checkpoint modulators in the treatment of glioblastoma. Nat Rev Neurol. 2015;11(9):504-514. doi: 10.1038/nrneurol.2015.139

 

  1. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. [published correction appears in N Engl J Med. 2010;363(13):1290]. N Engl J Med. 2010;363(8):711-723. doi: 10.1056/NEJMoa1003466

 

  1. O’Day SJ, Maio M, Chiarion-Sileni V, et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: A multicenter single-arm phase II study. Ann Oncol. 2010;21(8):1712-1717. doi: 10.1093/annonc/mdq013

 

  1. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454. doi: 10.1056/NEJMoa1200690

 

  1. Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for metastatic renal cell carcinoma: Results of a randomized phase II trial. J Clin Oncol. 2015;33(13):1430-1437. doi: 10.1200/jco.2014.59.0703

 

  1. Rizvi NA, Mazières J, Planchard D, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (checkmate 063): A phase 2, single-arm trial. Lancet Oncol. 2015;16(3):257-265. doi: 10.1016/s1470-2045(15)70054-9

 

  1. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus Ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381(21):2020-2031. doi: 10.1056/NEJMoa1910231

 

  1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and Ipilimumab in advanced melanoma. New Engl J Med. 2019;381(16):1535-1546. doi: 10.1056/nejmoa1910836

 

  1. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and Ipilimumab in advanced melanoma. New Engl J Med. 2017;377(14): 1345-1356. doi: 10.1056/nejmoa1709684

 

  1. Omuro A, Reardon DA, Sampson JH, et al. Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of checkmate 143. Neurooncol Adv. 2022;4(1):vdac025. doi: 10.1093/noajnl/vdac025

 

  1. Reardon DA, Kim TM, Frenel J, et al. Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE‐028 trial. Cancer. 2021;127(10):1620-1629. doi: 10.1002/cncr.33378

 

  1. Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98-106. doi: 10.1097/coc.0000000000000239

 

  1. Bloch O, Crane CA, Kaur R, Safaee M, Rutkowski MJ, Parsa AT. Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res. 2013;19(12):3165-3175. doi: 10.1158/1078-0432.ccr-12-3314

 

  1. Moyes KW, Davis A, Hoglund V, et al. Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma. OncoImmunology. 2018;7(11):e1507668. doi: 10.1080/2162402x.2018.1507668

 

  1. Abikenari M, Schonfeld E, Choi J, Kim LH, Lim M. Revisiting glioblastoma classification through an immunological lens: A narrative review. Glioma. 2024;7(2):3-9. doi: 10.4103/glioma.glioma_4_24

 

  1. Berghoff AS, Kiesel B, Widhalm G, et al. Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro Oncol. 2014;17(8):1064-1075. doi: 10.1093/neuonc/nou307

 

  1. Fecci PE, Mitchell DA, Whitesides JF, et al. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 2006;66(6):3294-3302. doi: 10.1158/0008-5472.can-05-3773

 

  1. Ampie L, Woolf EC, Dardis C. Immunotherapeutic advancements for glioblastoma. Front Oncol. 2015;5:12. doi: 10.3389/fonc.2015.00012

 

  1. Weller M, Kaulich K, Hentschel B, et al. Assessment and prognostic significance of the epidermal growth factor receptor vIII mutation in glioblastoma patients treated with concurrent and adjuvant temozolomide radiochemotherapy. [published correction appears in Int J Cancer. 2016 Aug 15;139(4):E9. doi: 10.1002/ijc.30155]. Int J Cancer. 2014;134(10):2437-2447. doi: 10.1002/ijc.28576

 

  1. Powers MV, Jones K, Barillari C, Westwood I, van Montfort RL, Workman P. Targeting HSP70: The second potentially druggable heat shock protein and molecular chaperone? Cell Cycle. 2010;9(8):1542-1550. doi: 10.4161/cc.9.8.11204

 

  1. Smaglo BG, Aldeghaither D, Weiner LM. The development of immunoconjugates for targeted cancer therapy. Nat Rev Clin Oncol. 2014;11(11):637-648. doi: 10.1038/nrclinonc.2014.159

 

  1. Young JC, Agashe VR, Siegers K, Hartl FU. Pathways of chaperone-mediated protein folding in the cytosol. Nat Rev Mol Cell Biol. 2004;5(10):781-791. doi: 10.1038/nrm1492

 

  1. Ampie L, Choy W, Lamano JB, Fakurnejad S, Bloch O, Parsa AT. Heat shock protein vaccines against glioblastoma: From bench to bedside. J Neuro Oncol. 2015;123(3):441-448. doi: 10.1007/s11060-015-1837-7

 

  1. Graner MW, Bigner DD. Chaperone proteins and brain tumors: Potential targets and possible therapeutics. Neuro Oncol. 2005;7(3):260-278. doi: 10.1215/S1152851704001188

 

  1. Srivastava PK, DeLeo AB, Old LJ. Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc Natl Acad Sci U S A. 1986;83(10):3407-3411. doi: 10.1073/pnas.83.10.3407

 

  1. Ullrich SJ, Robinson EA, Law LW, Willingham M, Appella E. A mouse tumor-specific transplantation antigen is a heat shock-related protein. Proc Natl Acad Sci U S A. 1986;83(10):3121-3125. doi: 10.1073/pnas.83.10.3121

 

  1. Schirrmacher V, Haas C, Bonifer R, Ahlert T, Gerhards R, Ertel C. Human tumor cell modification by virus infection: An efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties when using Newcastle disease virus. Gene Ther. 1999;6(1):63-73. doi: 10.1038/sj.gt.3300787

 

  1. Sampson JH, Heimberger AB, Archer GE, et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010;28(31):4722-4729. doi: 10.1200/JCO.2010.28.6963

 

  1. Batra SK, Castelino-Prabhu S, Wikstrand CJ, et al. Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene. Cell Growth Differ. 1995;6(10):1251-1259.

 

  1. Boockvar JA, Kapitonov D, Kapoor G, et al. Constitutive EGFR signaling confers a motile phenotype to neural stem cells. Mol Cell Neurosci. 2003;24(4):1116-1130. doi: 10.1016/j.mcn.2003.09.011

 

  1. Chu CT, Everiss KD, Wikstrand CJ, Batra SK, Kung HJ, Bigner DD. Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII). Biochem J. 1997;324(Pt 3): 855-861. doi: 10.1042/bj3240855

 

  1. Heimberger AB, Hlatky R, Suki D, et al. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res. 2005;11(4):1462-1466. doi: 10.1158/1078-0432.CCR-04-1737

 

  1. Hottinger AF, Stupp R, Homicsko K. Standards of care and novel approaches in the management of glioblastoma multiforme. Chin J Cancer. 2014;33(1):32-39. doi: 10.5732/cjc.013.10207

 

  1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996. doi: 10.1056/NEJMoa043330

 

  1. Giese A, Bjerkvig R, Berens ME, Westphal M. Cost of migration: Invasion of malignant gliomas and implications for treatment. J Clin Oncol. 2003;21(8):1624-1636. doi: 10.1200/JCO.2003.05.063

 

  1. Tzeng SY, Green JJ. Therapeutic nanomedicine for brain cancer. Ther Deliv. 2013;4(6):687-704. doi: 10.4155/tde.13.38

 

  1. Diehn M, Nardini C, Wang DS, et al. Identification of noninvasive imaging surrogates for brain tumor gene-expression modules. Proc Natl Acad Sci U S A. 2008;105(13):5213-5218. doi: 10.1073/pnas.0801279105

 

  1. Maher EA, Brennan C, Wen PY, et al. Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities. Cancer Res. 2006;66(23):11502-11513. doi: 10.1158/0008-5472.CAN-06-2072

 

  1. Mischel PS, Nelson SF, Cloughesy TF. Molecular analysis of glioblastoma: Pathway profiling and its implications for patient therapy. Cancer Biol Ther. 2003;2(3):242-247. doi: 10.4161/cbt.2.3.369

 

  1. Dubois LG, Campanati L, Righy C, et al. Gliomas and the vascular fragility of the blood brain barrier. Front Cell Neurosci. 2014;8:418. doi: 10.3389/fncel.2014.00418

 

  1. Monteiro AR, Hill R, Pilkington GJ, Madureira PA. The role of hypoxia in glioblastoma invasion. Cells. 2017;6(4):45. doi: 10.3390/cells6040045

 

  1. Urbańska K, Sokołowska J, Szmidt M, Sysa P. Glioblastoma multiforme - an overview. Contemp Oncol (Pozn). 2014;18(5):307-312. doi: 10.5114/wo.2014.40559

 

  1. Thakur A, Faujdar C, Sharma R, et al. Glioblastoma: Current status, emerging targets, and recent advances. J Med Chem. 2022;65(13):8596-8685. doi: 10.1021/acs.jmedchem.1c01946

 

  1. Arévalo ÁST, Erices JI, Uribe DA, et al. Current therapeutic alternatives and new perspectives in glioblastoma multiforme. Curr Med Chem. 2017;24(25):2781-2795. doi: 10.2174/0929867324666170303122241

 

  1. Fernandes GFD, Fernandes BC, Valente V, Dos Santos JL. Recent advances in the discovery of small molecules targeting glioblastoma. Eur J Med Chem. 2019;164:8-26. doi: 10.1016/j.ejmech.2018.12.033

 

  1. Khaddour K, Johanns TM, Ansstas G. The landscape of novel therapeutics and challenges in glioblastoma multiforme: Contemporary state and future directions. Pharmaceuticals (Basel). 2020;13(11):389. doi: 10.3390/ph13110389

 

  1. Zahonero C, Aguilera P, Ramírez-Castillejo C, et al. Preclinical test of dacomitinib, an irreversible EGFR inhibitor, confirms its effectiveness for glioblastoma. Mol Cancer Ther. 2015;14(7):1548-1558. doi: 10.1158/1535-7163.MCT-14-0736

 

  1. Hamed HA, Tavallai S, Grant S, Poklepovic A, Dent P. Sorafenib/regorafenib and lapatinib interact to kill CNS tumor cells. J Cell Physiol. 2015;230(1):131-139. doi: 10.1002/jcp.24689

 

  1. Haynik DM, Roma AA, Prayson RA. HER-2/neu expression in glioblastoma multiforme. Appl Immunohistochem Mol Morphol. 2007;15(1):56-58. doi: 10.1097/01.pai.0000213133.09160.da

 

  1. Lankheet NA, Hillebrand MJ, Rosing H, Schellens JH, Beijnen JH, Huitema AD. Method development and validation for the quantification of dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma by liquid chromatography coupled with tandem mass spectrometry. Biomed Chromatogr. 2013;27(4):466-476. doi: 10.1002/bmc.2814

 

  1. Sminia P, Westerman BA. Blood-brain barrier crossing and breakthroughs in glioblastoma therapy. Br J Clin Pharmacol. 2016;81(6):1018-1020. doi: 10.1111/bcp.12881

 

  1. Łazewska D, Wiecek M, Ligneau X, et al. Histamine H3 and H4 receptor affinity of branched 3-(1H-imidazol- 4-yl)propyl N-alkylcarbamates. Bioorg Med Chem Lett. 2009;19(23):6682-6685. doi: 10.1016/j.bmcl.2009.10.005

 

  1. Wang D, Wang C, Wang L, Chen Y. A comprehensive review in improving delivery of small-molecule chemotherapeutic agents overcoming the blood-brain/brain tumor barriers for glioblastoma treatment. Drug Deliv. 2019;26(1):551-565. doi: 10.1080/10717544.2019.1616235
Share
Back to top
Microbes & Immunity, Electronic ISSN: 3029-2883 Print ISSN: 3041-0886, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept