====== Glioma treatment ====== Significant effort has been made to investigate [[immunotherapy]] and [[precision oncology]] approaches. While there are many promising treatment strategies, none fundamentally changed the management of glioma patients. However, we are still awaiting the outcome of ongoing trials, which have the potential to revolutionize the treatment of glioma ((Śledzińska P, Bebyn M, Furtak J, Koper A, Koper K. Current and promising treatment strategies in glioma. Rev Neurosci. 2022 Sep 6. doi: 10.1515/revneuro-2022-0060. Epub ahead of print. PMID: 36062548.)). ---- [[Window of opportunity clinical trial]] designs can provide early insight into the biological plausibility of a novel therapeutic [[strategy]] in the clinical setting. A variety of window-of-opportunity trial designs, which take into account the limited access to treated [[tissue]] and the challenges with obtaining pretreatment control tissues, have been used for the initial development of traditional and targeted small-molecule [[drug]]s and biologic therapies, including immunotherapies and oncolytic viral therapies. Early-stage development of [[glioma treatment]] should include a window-of-opportunity component whenever feasible ((Vogelbaum MA, Li G, Heimberger AB, Lang FF, Fueyo J, Gomez-Manzano C, Sanai N. A [[Window of Opportunity]] to Overcome Therapeutic [[Failure]] in [[Neuro-Oncology]]. Am Soc Clin Oncol Educ Book. 2022 Apr;42:1-8. doi: 10.1200/EDBK_349175. PMID: 35580289.)). ---- [[4-methylumbelliferone]] (4-MU), a small competitive inhibitor of [[Uridine diphosphate]] (UDP) with the ability to penetrate the [[blood-brain barrier]] (BBB), inhibited [[glioma cell]] proliferation [[in vitro]] and [[in vivo]]. Thus, approaches that interfere with [[Hyaluronic acid]] metabolism by altering the expression of [[HAS3]] and [[CD44]] and the administration of 4-MU potentially represent effective strategies for [[glioma treatment]] ((Yan T, Chen X, Zhan H, Yao P, Wang N, Yang H, Zhang C, Wang K, Hu H, Li J, Sun J, Dong Y, Lu E, Zheng Z, Zhang R, Wang X, Ma J, Gao M, Ye J, Wang X, Teng L, Liu H, Zhao S. Interfering with [[hyaluronic acid]] metabolism suppresses [[glioma cell]] proliferation by regulating [[autophagy]]. Cell Death Dis. 2021 May 13;12(5):486. doi: 10.1038/s41419-021-03747-z. PMID: 33986244.)). ---- Recent advances in [[translational research]] and [[molecular]] understanding of [[brain tumor]]s raise hope that new [[treatment]]s are imminent, and patients should be encouraged to participate in [[clinical trial]]s. The general practitioners (GPs) has an important role in patient support and coordination of care ((Jeffree RL. Current management of cerebral gliomas. Aust J Gen Pract. 2020 Apr;49(4):194-199. doi: 10.31128/AJGP-09-19-5063. PubMed PMID: 32233347. )). Molecularly-targeted therapy is a focus of glioma research. Current standard treatment for [[glioma]] patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of [[tyrosine kinase receptor]]s including [[EGFR]], [[PDGFR]] and other crucial signal pathways such as [[PI3K]]/[[AKT]] and [[RAS]]/[[RAF]]/[[MAPK]] pathway. Furthermore, recent advances in targeting [[immunotherapy]] and [[stem cell therapy]] also brought numerous strategies to glioma treatment ((Lin L, Cai J, Jiang C. Recent advances in targeted therapy for glioma. Curr Med Chem. 2016 Dec 23. [Epub ahead of print] PubMed PMID: 28019637. )). ---- Evidence have shown that a recombinant adenoviral vector expressing human wild-type p53, granulocyte-macrophage colony-stimulating factor (GM-CSF), and B7-1 genes (BB-102) may have antitumor effects in vitro. In this study, we investigated the effects of BB-102-based vaccine on glioma in vivo. An animal model using nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with human immune system was established. The mice were vaccinated with inactivated U251 glioma cells transduced with BB-102 or adenoviral vector expressing green fluorescence protein (Ad-GFP) as a control and followed by the challenge of live U251 glioma cells. Tumor growth and antitumor responses were measured. Data showed that mice vaccinated with BB-102 had significantly reduced local tumor growth compared to mice with Ad-GFP vaccination or the control group. Histopathological analysis displayed low tumor cell density and significant infiltration of human peripheral blood lymphocytes (HuPBLs) in the tumor tissues of mice transduced with BB-102. Immunohistochemical analysis showed that mutant p53 was not expressed in tumor tissues of mice with BB-102 vaccination, and the expression level of Ki67 was significantly lower in the tumor tissues of the BB-102 group than those in the Ad-GFP group or the control group. Further study demonstrated that mice with BB-102 vaccination had significantly increased total T cell numbers, total T cell proportion, CD4+ T cell proportion, and CD8+ T cell proportion in spleens, as well as higher value of IgG, IgA, and IgE in sera. These data suggest that the recombinant adenoviral vector expressing human wild-type p53, GM-CSF, and B7-1 genes could suppress glioma in NOD/SCID mice model and might be considered as a novel strategy for glioma therapy ((Feng S, Han S, Pan D, Liu M, Feng X, Dong T, Li W, Wei X. Recombinant adenoviral vector expressing human wild-type p53, GM-CSF, and B7-1 genes suppresses the growth of glioma in vivo. Tumour Biol. 2014 Jan 10. [Epub ahead of print] PubMed PMID: 24408016.)). ---- Treatment options depend on the type of glioma, and patient-specific factors such as location and size of the glioma, patient age, symptoms and neurological status. In addition, three molecular markers – 1p/19q co-deletion, O6-methylguanine methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) 1/2 mutations – are known to have important diagnostic, prognostic and predictive (for treatment efficacy) roles in glioma treatment (for reviews see Tabatabai et al. 2010 ((Tabatabai G, Stupp R, van den Bent MJ, Hegi ME, Tonn JC, Wick W, et al. Molecular diagnostics of gliomas: the clinical perspective. Acta Neuropathol. 2010;120(5):585–92.)) and Leu et al. ((Leu S, von Felten S, Frank S, Vassella E, Vajtai I, Taylor E, et al. IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival. Neuro Oncol. 2013;15(4):469–79. doi: 10.1093/neuonc/nos317.)). ---- The therapeutic management and prognosis of cerebral gliomas depend on tumor type and grade, and on exact definition of boundary ((Behin A, Hoang-Xuan K, Carpentier AF, Delattre J-Y (2003) Primary brain tumours in adults. Lancet 361:323–331)) ((Grant R (2004) Overview: brain tumour diagnosis and management/Royal College of Physicians guidelines. J Neurol Neurosurg Psychiatry 75 [Suppl 2]:II18–II23)) ((Schneider JP, Trantakis C, Rubach M, et al (2005) Intraoperative MRI to guide the resection of primary supratentorial glioblastoma multiforme – a quantitative radiological analysis. Neuroradiology 47:489–500)). In glioma patients, a presumed [[eloquent]] location has been identified as a key variable influencing the treatment strategy ((Jakola AS, Unsgård G,Myrmel KS, et al. Low-grade gliomas in eloquent locations - implications for surgical strategy, survival and long term quality of life. PLoS One 2012;7(12):e51450.)) ((Seiz M, Freyschlag CF, Schenkel S, et al. Management of patients with low-grade gliomas - a survey among German neurosurgical departments. Cen Eur Neurosurg 2011;72(4):186-191.)). ===== Surgery ===== see [[Glioma surgery]] ===== High-grade glioma treatment ===== see [[High-grade glioma treatment]]. ===== Glioma immunotherapy ===== [[Glioma immunotherapy]]. ===== Glioma Radiosurgery ===== [[Glioma Radiosurgery]].