Integrating and optimizing tonabersat in standard glioblastoma therapy: A preclinical study.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2024
2024
Historique:
received:
09
01
2024
accepted:
28
02
2024
medline:
18
3
2024
pubmed:
15
3
2024
entrez:
15
3
2024
Statut:
epublish
Résumé
Glioblastoma (GB), a highly aggressive primary brain tumor, presents a poor prognosis despite the current standard therapy, including radiotherapy and temozolomide (TMZ) chemotherapy. Tumor microtubes involving connexin 43 (Cx43) contribute to glioma progression and therapy resistance, suggesting Cx43 inhibition as a potential treatment strategy. This research aims to explore the adjuvant potential of tonabersat, a Cx43 gap junction modulator and blood-brain barrier-penetrating compound, in combination with the standard of care for GB. In addition, different administration schedules and timings to optimize tonabersat's therapeutic window are investigated. The F98 Fischer rat model will be utilized to investigate tonabersat's impact in a clinically relevant setting, by incorporating fractionated radiotherapy (three fractions of 9 Gy) and TMZ chemotherapy (29 mg/kg). This study will evaluate tonabersat's impact on tumor growth, survival, and treatment response through advanced imaging (CE T1-w MRI) and histological analysis. Results show extended survival in rats receiving tonabersat with standard care, highlighting its adjuvant potential. Daily tonabersat administration, both preceding and following radiotherapy, emerges as a promising approach for maximizing survival outcomes. The study suggests tonabersat's potential to reduce tumor invasiveness, providing a new avenue for GB treatment. In conclusion, this preclinical investigation highlights tonabersat's potential as an effective adjuvant treatment for GB, and its established safety profile from clinical trials in migraine treatment presents a promising foundation for further exploration.
Identifiants
pubmed: 38489314
doi: 10.1371/journal.pone.0300552
pii: PONE-D-24-01093
pmc: PMC10942024
doi:
Substances chimiques
tonabersat
2XD9773ZMN
Connexin 43
0
Temozolomide
YF1K15M17Y
Antineoplastic Agents, Alkylating
0
Benzamides
0
Benzopyrans
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0300552Informations de copyright
Copyright: © 2024 Zoteva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Neoplasia. 2010 Sep;12(9):748-54
pubmed: 20824051
Epilepsia. 2013 Dec;54 Suppl 9:12-7
pubmed: 24328866
Nat Rev Dis Primers. 2015 Jul 16;1:15017
pubmed: 27188790
Biochim Biophys Acta. 2012 Aug;1818(8):2058-67
pubmed: 22063721
Bull Exp Biol Med. 2012 May;153(1):163-9
pubmed: 22808518
Nat Rev Cancer. 2016 Dec;16(12):775-788
pubmed: 27782134
Epilepsy Res. 2013 Jan;103(1):2-30
pubmed: 23219031
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Theranostics. 2020 Feb 10;10(7):3223-3239
pubmed: 32194864
Int J Prev Med. 2013 Jun;4(6):624-30
pubmed: 23930179
Neurotherapeutics. 2020 Jan;17(1):371-387
pubmed: 31637594
Oncogene. 2019 Jun;38(23):4429-4451
pubmed: 30814684
Neurotherapeutics. 2017 Oct;14(4):1148-1165
pubmed: 28560708
PLoS One. 2019 Oct 21;14(10):e0224130
pubmed: 31634381
Bull Exp Biol Med. 2014 Aug;157(4):510-5
pubmed: 25110095
Acta Neuropathol. 1980;51(1):23-31
pubmed: 7435138
Zh Vopr Neirokhir Im N N Burdenko. 2015;79(3):15-26
pubmed: 26529530
Oncogene. 2016 Mar 24;35(12):1504-16
pubmed: 26165844
Int J Mol Sci. 2023 Feb 15;24(4):
pubmed: 36835288
Biochim Biophys Acta. 2004 Mar 23;1662(1-2):149-58
pubmed: 15033585
Clin Cancer Res. 2013 Feb 15;19(4):764-72
pubmed: 23209033
Cancer Res. 1999 Apr 15;59(8):1994-2003
pubmed: 10213512
Cancer Res. 2014 Sep 1;74(17):4622-4637
pubmed: 25183787
Front Oncol. 2021 Feb 05;10:574012
pubmed: 33614476
Neuro Oncol. 2018 Jun 18;20(7):885-896
pubmed: 29106645
Cephalalgia. 2009 Nov;29 Suppl 2:28-35
pubmed: 19723123
Front Oncol. 2018 Dec 21;8:646
pubmed: 30622930
Iran J Med Sci. 2017 May;42(3):258-265
pubmed: 28533574
Nature. 2015 Dec 3;528(7580):93-8
pubmed: 26536111
Expert Rev Clin Pharmacol. 2013 May;6(3):333-44
pubmed: 23656344
Int J Mol Sci. 2020 Sep 23;21(19):
pubmed: 32977526
Can J Neurol Sci. 2006 Feb;33(1):86-91
pubmed: 16583728
Neuro Oncol. 2016 Jun;18(6):779-89
pubmed: 26527735
Nat Neurosci. 2019 Dec;22(12):1951-1960
pubmed: 31719671
PLoS One. 2024 Jan 2;19(1):e0296360
pubmed: 38165944
Acta Neurochir (Wien). 1986;79(1):35-41
pubmed: 3953322
J Biomed Phys Eng. 2022 Feb 01;12(1):43-50
pubmed: 35155292
J Neurooncol. 2009 Sep;94(3):299-312
pubmed: 19381449
BMC Cell Biol. 2005 Feb 16;6(1):7
pubmed: 15715906
Neurol Clin. 2009 May;27(2):335-60
pubmed: 19289219
Int J Mol Sci. 2018 Apr 11;19(4):
pubmed: 29641478
Nature. 2016 May 18;533(7604):493-498
pubmed: 27225120
J Clin Oncol. 2006 Aug 20;24(24):3823-30
pubmed: 16921033
Neuro Oncol. 2021 Aug 2;23(8):1231-1251
pubmed: 34185076
Wiley Interdiscip Rev Membr Transp Signal. 2013 Jan;2(1):1-15
pubmed: 23565352
Malays J Med Sci. 2017 Oct;24(5):101-105
pubmed: 29386977
Bull Math Biol. 2018 May;80(5):1207-1235
pubmed: 29488054
J Neuropathol Exp Neurol. 2022 Apr 27;81(5):312-329
pubmed: 35446393
Mol Cancer Res. 2022 Feb;20(2):319-331
pubmed: 34654721
Clin Transl Oncol. 2016 Nov;18(11):1062-1071
pubmed: 26960561
Nature. 2009 Feb 5;457(7230):675-7
pubmed: 19194443
Front Physiol. 2014 May 16;5:186
pubmed: 24904426
J Pharmacol Pharmacother. 2013 Oct;4(4):303-6
pubmed: 24250214
Int J Mol Sci. 2020 Dec 31;22(1):
pubmed: 33396284
Oncotarget. 2015 Jun 20;6(17):15566-77
pubmed: 25978028
Headache. 2009 Jan;49(1):5-20
pubmed: 19125874
Neuro Oncol. 2016 Apr;18(4):479-85
pubmed: 26995789
Adv Exp Med Biol. 2016;949:1-24
pubmed: 27714682