Perspectieven inzake 
het glioblastoom

Het glioblastoom is de agressiefste tumor van het centrale zenuwstelsel. Ondanks een goed omschreven multimodale behandeling, zal de tumor in de regel recidiveren en is de overleving van de patiënten zelden langer dan 18-24 maanden. Daarom onderzoeken veel vorsers de fundamentele biologie van die tumor, die nooit meta‑
staseert, en exploreren artsen nieuwe therapeutische benaderingen. We geven hier een kort overzicht van de recente gegevens over de biologie van de glioblastoomcellen en van de nieuwe behandelingen die de laatste jaren zijn ontwikkeld.

> Indien u hierover meer wenst te weten, dan verwijzen wij u graag naar de integrale tekst.

  • Laboratory of Nervous System Disorders and Therapy, GIGA-Neurosciences Research Center, ULg; Dienst neurologie, CHU de Liège

  • 1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-96.
    2. Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barmholtz-Sloan JS. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2011-2015. Neuro Oncol 2018;20:iv1-iv86.
    3. 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;131:803-20.
    4. Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clinical Cancer Res 2013;19:764-72.
    5. Verhaak RGW, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17:98-110.
    6. Brennan CW, Verhaak RG, McKenna A. et al. The somatic genomic landscape of glioblastoma. Cell 2013;155:462-77.
    7. Wang Q, Hu B, Hu X, et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell 2017;32:42-56.
    8. Sottoriva A, Spiteri I, Piccirillo SG, et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci 2013;110:4009-14.
    9. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
    10. Batlle E, Clevers H. Cancer stem cells revisited. Nat.Med 2017;23:1124-34.
    11. Ignatova TN, Kukelov VG, Laywell ED, Suslov ON, Vrionis FD, Steindler DA. Human cortical glial tumors contain neural stem‐like cells expressing astroglial and neuronal markers in vitro. Glia 2002;39:193-206.
    12. Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN. Cancer stem cells in glioblastoma. Genes Dev 2015;29:1203-17.
    13. Lombard A, Goffart N, Rogister B. Glioblastoma circulating cells: reality, trap or illusion? Stem Cells Int 2015: 182985.
    14. Stupp R, Hegi ME. Targeting brain-tumor stem cells. Nat Biotechnol 2007;25:193.
    15. Bao S. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006;444:756.
    16. Uribe D, Torres A, Rochas JD, et al. Multidrug resistance in glioblastoma stem-like cells: Role of the hypoxic microenvironment and adenosine signaling. Mol Aspects Med 2017;55:140-51.
    17. Blough MD, Westgate MR, Beauchamps D, et al. Sensitivity to temozolomide in brain tumor initiating cells. Neuro-Oncol 2010;12:756-60.
    18. Lee JH, Lee JE, Kahng JY, et al. Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature 2018;560:243-7.
    19. García-Marqués J, Núñez-Llaves R, López-Mascaraque L. NG2-glia from pallial progenitors produce the largest clonal clusters of the brain: time frame of clonal generation in cortex and olfactory bulb. J Neurosci 2014;34:2305-13.
    20. Alcantara Llaguno SR, Wang Z, Sun D, et al. Adult lineage-restricted CNS progenitors specify distinct glioblastoma subtypes. Cancer Cell 2015;28:429-40.
    21. Persson AI, Petritsch C, Swartling FJ, et al. Non-stem cell origin for oligodendroglioma. Cancer Cell 2010;18:669-82.
    22. Rutledge WC, Kong J, Gao J, et al. Tumor-infiltrating lymphocytes in glioblastoma are associated with specific genomic alterations and related to transcriptional class. Clin Cancer Res 2013;19:4951-60.
    23. Razavi SM, Lee KE, Jin BE, Aujla PS, Gholamin S, Li G. Immune evasion strategies of Glioblastoma. Front Surg 2016;2,3:11.
    24. Kurz SC, Cabrera LP, Hastie D, et al. PD-1 inhibition has limited clinical benefit in patients with recurrent high-grade glioma. Neurology 2018;91:e1355-e1359.
    25. Zhang M, Ye G, Wang Y. Recent advance in molecular angiogenesis in glioblastoma: the challenge and hope for anti-angiogenic therapy. Brain Tumor Pathol 2015;32:229-36.
    26. Wick W, Gorlia T, Bendszus M, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med 2017;377:1954-63.
    27. Malkki H. Trial Watch: Glioblastoma vaccine therapy disappointment in phase III trial. Nat Rev Neurol 2016;12:190.
    28. Maxwell R, Luksik AS, Garzon-Muvdi T, lim M. The potential of cellular and viral-based immunotherapies for malignant glio-dendritic cell vaccines, adoptive cell transfer and oncolytic virus. Curr Neurol Neurosci Rep 2017;17:50.
    29. Burri SH, Gondi V, Brown PD, Mehta MP. The evolving role of tumor treating fields in managing glioblastoma: guide for oncologists. Am J Clin Oncol Cancer Clin Trials 2018;41:191-6.
    30. Touat M, Idbaih A, Sanson M, Ligon KL. Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann Oncol 2017;28:1457-72.

U wil op dit artikel reageren ?

Toegang tot alle functionaliteiten is gereserveerd voor professionele zorgverleners.

Indien u een professionele zorgverlener bent, dient u zich aan te melden of u gratis te registreren om volledige toegang te krijgen tot deze inhoud.
Bent u journalist of wenst u ons te informeren, schrijf ons dan op