Wybrane innowacje w terapii glejaków

Autorzy

Maciej Baron - ; Andrzej Skrzypiec - ; Bartosz Bula - ; Maciej Czwakiel - ; Marcin Fyrla -

Słowa kluczowe:

glejak mózgu, glejak wielopostaciowy, immunoterapia, onkologia

Streszczenie

Abstrakt 

Glejaki to heterogenna grupa nowotworów ośrodkowego układu nerwowego, stanowiąca obecnie poważne wyzwanie kliniczne. Szacuje się, że zapadalność na guzy mózgu w Polsce wynosi od 7 do 8 przypadków na 100 000 mieszkańców rocznie. Z uwagi na ich agresywny przebieg oraz ograniczoną skuteczność dostępnych metod leczenia, glejaki są przedmiotem intensywnych badań naukowych. Poszukuje się nowych biomarkerów, które mogłyby usprawnić diagnostykę, a także innowacyjnych strategii terapeutycznych, zdolnych zastąpić lub uzupełnić dotychczasowe, niewystarczające podejścia. Niniejszy przegląd ma na celu podsumowanie aktualnego stanu wiedzy dotyczącej patogenezy, diagnostyki oraz leczenia glejaków. 

 

 

Abstract 

Gliomas are a heterogeneous group of central nervous system tumors that currently represent a significant clinical challenge. It is estimated that the incidence of brain tumors in Poland ranges from 7 to 8 cases per 100,000 inhabitants per year. Due to their aggressive course and the limited effectiveness of available treatments, gliomas are the subject of intensive scientific research. Efforts are being made to identify new biomarkers that could improve the diagnostic process, as well as to develop innovative therapeutic strategies capable of replacing or complementing current, insufficient approaches. This review aims to summarize the current state of knowledge regarding the pathogenesis, diagnosis, and treatment of gliomas. 

 

Bibliografia

Schneider T, Mawrin C, Scherlach C, Skalej M, Firsching R. Gliomas in adults. Dtsch Arztebl Int. 2010;107(45):799-808. doi:10.3238/arztebl.2010.0799

Lee SC. Diffuse Gliomas for Nonneuropathologists: The New Integrated Molecular Diagnostics. Arch Pathol Lab Med. 2018;142(7):804-814. doi:10.5858/arpa.2017-0449-RA

Sejda A, Grajkowska W, Trubicka J, et al. WHO CNS5 2021 classification of gliomas: a practical review and road signs for diagnosing pathologists and proper patho-clinical and neuro-oncological cooperation. Folia Neuropathol. 2022;60(2):137-152. doi:10.5114/fn.2022.118183

Miller JJ. Targeting IDH-Mutant Glioma. Neurotherapeutics. 2022;19(6):1724-1732. doi:10.1007/s13311-022-01238-3

Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system [published correction appears in Acta Neuropathol. 2007 Nov;114(5):547]. Acta Neuropathol. 2007;114(2):97-109. doi:10.1007/s00401-007-0243-4

Barami K. Oncomodulatory mechanisms of human cytomegalovirus in gliomas. J Clin Neurosci. 2010;17(7):819-823. doi:10.1016/j.jocn.2009.10.040

Smoll NR, Brady Z, Scurrah K, Mathews JD. Exposure to ionizing radiation and brain cancer incidence: The Life Span Study cohort. Cancer Epidemiol. 2016;42:60-65. doi:10.1016/j.canep.2016.03.006

Berg-Beckhoff G, Schüz J, Blettner M, et al. History of allergic disease and epilepsy and risk of glioma and meningioma (INTERPHONE study group, Germany). Eur J Epidemiol. 2009;24(8):433-440. doi:10.1007/s10654-009-9355-6

Wigertz A, Lönn S, Schwartzbaum J, et al. Allergic conditions and brain tumor risk. Am J Epidemiol. 2007;166(8):941-950. doi:10.1093/aje/kwm203

Held K, Voets T, Vriens J. TRPM3 in temperature sensing and beyond. Temperature (Austin). 2015;2(2):201-213. Published 2015 Feb 25. doi:10.4161/23328940.2014.988524

Wong KK, Banham AH, Yaacob NS, Nur Husna SM. The oncogenic roles of TRPM ion channels in cancer. J Cell Physiol. 2019;234(9):14556-14573. doi:10.1002/jcp.28168

Santoni G, Maggi F, Morelli MB, Santoni M, Marinelli O. Transient Receptor Potential Cation Channels in Cancer Therapy. Med Sci (Basel). 2019;7(12):108. Published 2019 Nov 30. doi:10.3390/medsci7120108

Chinigò G, Castel H, Chever O, Gkika D. TRP Channels in Brain Tumors. Front Cell Dev Biol. 2021;9:617801. Published 2021 Apr 13. doi:10.3389/fcell.2021.617801

Zhao Q, Li J, Ko WH, et al. TRPM2 promotes autophagic degradation in vascular smooth muscle cells. Sci Rep. 2020;10(1):20719. Published 2020 Nov 26. doi:10.1038/s41598-020-77620-y

Chen WL, Turlova E, Sun CL, et al. Xyloketal B suppresses glioblastoma cell proliferation and migration in vitro through inhibiting TRPM7-regulated PI3K/Akt and MEK/ERK signaling pathways. Mar Drugs. 2015;13(4):2505-2525. Published 2015 Apr 22. doi:10.3390/md13042505

Thuringer D, Chanteloup G, Winckler P, Garrido C. The vesicular transfer of CLIC1 from glioblastoma to microvascular endothelial cells requires TRPM7. Oncotarget. 2018;9(70):33302-33311. Published 2018 Sep 7. doi:10.18632/oncotarget.26048

Zalles M, Smith N, Saunders D, et al. A tale of two multi-focal therapies for glioblastoma: An antibody targeting ELTD1 and nitrone-based OKN-007. J Cell Mol Med. 2022;26(2):570-582. doi:10.1111/jcmm.17133

Klumpp D, Frank SC, Klumpp L, et al. TRPM8 is required for survival and radioresistance of glioblastoma cells. Oncotarget. 2017;8(56):95896-95913. Published 2017 Sep 30. doi:10.18632/oncotarget.21436

Melhuish TA, Gallo CM, Wotton D. TGIF2 interacts with histone deacetylase 1 and represses transcription. J Biol Chem. 2001;276(34):32109-32114. doi:10.1074/jbc.M103377200

Zhang W, Zhang L, Dong H, Peng H. TGIF2 is a potential biomarker for diagnosis and prognosis of glioma. Front Immunol. 2024;15:1356833. Published 2024 Feb 26. doi:10.3389/fimmu.2024.1356833

Jiang J, Wu RH, Zhou HL, et al. TGIF2 promotes cervical cancer metastasis by negatively regulating FCMR. Eur Rev Med Pharmacol Sci. 2020;24(11):5953-5962. doi:10.26355/eurrev_202006_21488

Du R, Shen W, Liu Y, et al. TGIF2 promotes the progression of lung adenocarcinoma by bridging EGFR/RAS/ERK signaling to cancer cell stemness. Signal Transduct Target Ther. 2019;4:60. Published 2019 Dec 13. doi:10.1038/s41392-019-0098-x

Vinchure OS, Sharma V, Tabasum S, et al. Polycomb complex mediated epigenetic reprogramming alters TGF-β signaling via a novel EZH2/miR-490/TGIF2 axis thereby inducing migration and EMT potential in glioblastomas. Int J Cancer. 2019;145(5):1254-1269. doi:10.1002/ijc.32360

Zhang W, Zhang L, Dong H, Peng H. TGIF2 is a potential biomarker for diagnosis and prognosis of glioma. Front Immunol. 2024;15:1356833. Published 2024 Feb 26. doi:10.3389/fimmu.2024.1356833

Qu Y, Zhu J, Liu J, Qi L. Circular RNA circ_0079593 indicates a poor prognosis and facilitates cell growth and invasion by sponging miR-182 and miR-433 in glioma. J Cell Biochem. 2019;120(10):18005-18013. doi:10.1002/jcb.29103

Sun W, Zhou H, Han X, Hou L, Xue X. Circular RNA: A novel type of biomarker for glioma (Review). Mol Med Rep. 2021;24(2):602. doi:10.3892/mmr.2021.12240

Hua L, Huang L, Zhang X, Feng H, Shen B. Knockdown of circular RNA CEP128 suppresses proliferation and improves cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p. Neuroreport. 2019;30(18):1231-1238. doi:10.1097/WNR.0000000000001326

Dagher OK, Schwab RD, Brookens SK, Posey AD, Jr. Advances in cancer immunotherapies. Cell (2023) 186(8):1814–.e1. doi: 10.1016/j.cell.2023.02.039

Shi T, Song X, Wang Y, Liu F, Wei J. Combining oncolytic viruses with cancer immunotherapy: establishing a new generation of cancer treatment. Front Immunol (2020) 11:683. doi: 10.3389/fimmu.2020.00683

Lim M, Xia Y, Bettegowda C, Weller M. Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol (2018) 15(7):422–42. doi: 10.1038/s41571-018-0003-5

Sampson JH, Gunn MD, Fecci PE, Ashley DM. Brain immunology and immunotherapy in brain tumours. Nat Rev Cancer (2020) 20(1):12–25. doi: 10.1038/s41568-019-0224-7

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. doi: 10.3389/fimmu.2022.944452

Korman AJ, Garrett-Thomson SC, Lonberg N. The foundations of immune checkpoint blockade and the ipilimumab approval decennial. Nat Rev Drug Discovery (2022) 21(7):509–28. doi: 10.1038/s41573-021-00345-8

Ott PA, Hodi FS, Robert C. CTLA-4 and PD-1/PD-L1 blockade: new immunotherapeutic modalities with durable clinical benefit in melanoma patients. Clin Cancer Res (2013) 19(19):5300–9. doi: 10.1158/1078-0432.CCR-13-0143

Morton DL, Barth A. Vaccine therapy for Malignant melanoma. CA Cancer J Clin (1996) 46(4):225–44. doi: 10.3322/canjclin.46.4.225

Cunto-Amesty G, Monzavi-Karbassi B, Luo P, Jousheghany F, Kieber-Emmons T. Strategies in cancer vaccines development. Int J Parasitol (2003) 33(5-6):597–613. doi: 10.1016/S0020-7519(03)00054-7

Zhao B, Wu J, Li H, Wang Y, Wang Y, Xing H, et al. Recent advances and future challenges of tumor vaccination therapy for recurrent glioblastoma. Cell Commun Signal (2023) 21(1):74. doi: 10.1186/s12964-023-01098-0

Swartz AM, Batich KA, Fecci PE, Sampson JH. Peptide vaccines for the treatment of glioblastoma. J Neurooncol (2015) 123(3):433–40. doi: 10.1007/s11060-014-1676-y

Li L, Zhou J, Dong X, Liao Q, Zhou D, Zhou Y. Dendritic cell vaccines for glioblastoma fail to complete clinical translation: Bottlenecks and potential countermeasures. Int Immunopharmacol (2022) 109:108929. doi: 10.1016/j.intimp.2022.108929

Sayegh ET, Oh T, Fakurnejad S, Bloch O, Parsa AT. Vaccine therapies for patients with glioblastoma. J Neurooncol (2014) 119(3):531–46. doi: 10.1007/s11060-014-1502-6

Purcell AW, McCluskey J, Rossjohn J. More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discovery (2007) 6(5):404–14. doi: 10.1038/nrd2224

Sturm D, Bender S, Jones DT, Lichter P, Grill J, Becher O, et al. Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat Rev Cancer (2014) 14(2):92–107. doi: 10.1038/nrc3655

Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, et al. The somatic genomic landscape of glioblastoma. Cell (2013) 155(2):462–77. doi: 10.1016/j.cell.2013.09.034

Weller M, Kaulich K, Hentschel B, Felsberg J, Gramatzki D, Pietsch T, et al. Assessment and prognostic significance of the epidermal growth factor receptor vIII mutation in glioblastoma patients treated with concurrent and adjuvant temozolomide radiochemotherapy. Int J Cancer (2014) 134(10):2437–47. doi: 10.1002/ijc.28576

Huang PH, Mukasa A, Bonavia R, Flynn RA, Brewer ZE, Cavenee WK, et al. Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma. Proc Natl Acad Sci U S A (2007) 104(31):12867–72. doi: 10.1073/pnas.0705158104

Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol (2017) 18(10):1373–85. doi: 10.1016/S1470-2045(17)30517-X

Lee-Chang C, Lesniak MS. Next-generation antigen-presenting cell immune therapeutics for gliomas. J Clin Invest (2023) 133(3):e163449. doi: 10.1172/JCI163449

Bregy A, Wong TM, Shah AH, Goldberg JM, Komotar RJ. Active immunotherapy using dendritic cells in the treatment of glioblastoma multiforme. Cancer Treat Rev (2013) 39(8):891–907. doi: 10.1016/j.ctrv.2013.05.007

Wylie B, Macri C, Mintern JD, Waithman J. Dendritic cells and cancer: from biology to therapeutic intervention. Cancers (Basel) (2019) 11(4):521. doi: 10.3390/cancers11040521

Frederico SC, Hancock JC, Brettschneider EES, Ratnam NM, Gilbert MR, Terabe M. Making a cold tumor hot: the role of vaccines in the treatment of glioblastoma. Front Oncol (2021) 11:672508. doi: 10.3389/fonc.2021.672508

Zhang M, Choi J, Lim M. Advances in immunotherapies for gliomas. Curr Neurol Neurosci Rep (2022) 22(1):1–10. doi: 10.1007/s11910-022-01176-9

Liau LM, Ashkan K, Brem S, Campian JL, Trusheim JE, Iwamoto FM, et al. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: A phase 3 prospective externally controlled cohort trial. JAMA Oncol (2023) 9(1):112–21. doi: 10.1001/jamaoncol.2022.5370

Liau LM, Ashkan K, Tran DD, Campian JL, Trusheim JE, Cobbs CS, et al. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med (2018) 16(1):142. doi: 10.1186/s12967-018-1507-6

Chen D, Yang J. Development of novel antigen receptors for CAR T-cell therapy directed toward solid Malignancies. Transl Res (2017) 187:11–21. doi: 10.1016/j.trsl.2017.05.006

Li L, Zhu X, Qian Y, Yuan X, Ding Y, Hu D, et al. Chimeric antigen receptor T-cell therapy in glioblastoma: current and future. Front Immunol (2020) 11:594271. doi: 10.3389/fimmu.2020.594271

Bagley SJ, Desai AS, Linette GP, June CH, O'Rourke DM. CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges. Neuro Oncol (2018) 20(11):1429–38. doi: 10.1093/neuonc/noy032

O'Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med (2017) 9(399):eaaa0984. doi: 10.1126/scitranslmed.aaa0984

Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med (2016) 375(26):2561–9. doi: 10.1056/NEJMoa1610497

Ahmed N, Brawley V, Hegde M, Bielamowicz K, Kalra M, Landi D, et al. HER2-specific chimeric antigen receptor-modified virus-specific T cells for progressive glioblastoma: A phase 1 dose-escalation trial. JAMA Oncol (2017) 3(8):1094–101. doi: 10.1001/jamaoncol.2017.0184

Liu P, Wang Y, Wang Y, Kong Z, Chen W, Li J, et al. Effects of oncolytic viruses and viral vectors on immunity in glioblastoma. Gene Ther (2022) 29(3-4):115–26. doi: 10.1038/s41434-020-00207-9

Nguyen HM, Saha D. The current state of oncolytic herpes simplex virus for glioblastoma treatment. Oncolytic Virother (2021) 10:1–27. doi: 10.2147/OV.S268426

Qi Z, Long X, Liu J, Cheng P. Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy. Front Cell Neurosci (2022) 16:819363. doi: 10.3389/fncel.2022.819363

Martikainen M, Essand M. Virus-based immunotherapy of glioblastoma. Cancers (Basel) (2019) 11(2):186. doi: 10.3390/cancers11020186

Aurelian L. Oncolytic viruses as immunotherapy: progress and remaining challenges. Onco Targets Ther (2016) 9:2627–37. doi: 10.2147/OTT.S63049

Chiocca EA, Abbed KM, Tatter S, Louis DN, Hochberg FH, Barker F, et al. A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent Malignant gliomas, in the adjuvant setting. Mol Ther (2004) 10(5):958–66. doi: 10.1016/j.ymthe.2004.07.021

Zhu Z, Gorman MJ, McKenzie LD, Chai JN, Hubert CG, Prager BC, et al. Zika virus has oncolytic activity against glioblastoma stem cells. J Exp Med (2017) 214(10):2843–57. doi: 10.1084/jem.20171093

Jiang H, Gomez-Manzano C, Aoki H, Alonso MM, Kondo S, McCormick F, et al. Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death. J Natl Cancer Inst (2007) 99(18):1410–4. doi: 10.1093/jnci/djm102

Kanai R, Wakimoto H, Martuza RL, Rabkin SD. A novel oncolytic herpes simplex virus that synergizes with phosphoinositide 3-kinase/Akt pathway inhibitors to target glioblastoma stem cells. Clin Cancer Res (2011) 17(11):3686–96. doi: 10.1158/1078-0432.CCR-10-3142

Todo T, Ito H, Ino Y, Ohtsu H, Ota Y, Shibahara J, et al. Intratumoral oncolytic herpes virus G47Δ for residual or recurrent gli oblastoma: a phase 2 trial. Nat Med (2022) 28(8):1630–9. doi: 10.1038/s41591-022-01897-x

Opublikowane

6 sierpnia 2025