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Integrating and optimizing tonabersat in standard glioblastoma therapy : a preclinical study

Velislava Zoteva (UGent) , Valerie De Meulenaere (UGent) , Christian Vanhove (UGent) , Luc Leybaert (UGent) , Robrecht Raedt (UGent) , Leen Pieters (UGent) , Anne Vral (UGent) , Tom Boterberg (UGent) and Karel Deblaere (UGent)
(2024) PLOS ONE. 19(3).
Author
Organization
Abstract
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.
Keywords
GAP-JUNCTION PROTEIN, MONOCLONAL-ANTIBODIES, GLIOMA INVASION, CELL-LINES, RADIOTHERAPY, TEMOZOLOMIDE, FRAGMENT, CANCER

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MLA
Zoteva, Velislava, et al. “Integrating and Optimizing Tonabersat in Standard Glioblastoma Therapy : A Preclinical Study.” PLOS ONE, edited by Alexandre Hiroaki Kihara, vol. 19, no. 3, 2024, doi:10.1371/journal.pone.0300552.
APA
Zoteva, V., De Meulenaere, V., Vanhove, C., Leybaert, L., Raedt, R., Pieters, L., … Deblaere, K. (2024). Integrating and optimizing tonabersat in standard glioblastoma therapy : a preclinical study. PLOS ONE, 19(3). https://doi.org/10.1371/journal.pone.0300552
Chicago author-date
Zoteva, Velislava, Valerie De Meulenaere, Christian Vanhove, Luc Leybaert, Robrecht Raedt, Leen Pieters, Anne Vral, Tom Boterberg, and Karel Deblaere. 2024. “Integrating and Optimizing Tonabersat in Standard Glioblastoma Therapy : A Preclinical Study.” Edited by Alexandre Hiroaki Kihara. PLOS ONE 19 (3). https://doi.org/10.1371/journal.pone.0300552.
Chicago author-date (all authors)
Zoteva, Velislava, Valerie De Meulenaere, Christian Vanhove, Luc Leybaert, Robrecht Raedt, Leen Pieters, Anne Vral, Tom Boterberg, and Karel Deblaere. 2024. “Integrating and Optimizing Tonabersat in Standard Glioblastoma Therapy : A Preclinical Study.” Ed by. Alexandre Hiroaki Kihara. PLOS ONE 19 (3). doi:10.1371/journal.pone.0300552.
Vancouver
1.
Zoteva V, De Meulenaere V, Vanhove C, Leybaert L, Raedt R, Pieters L, et al. Integrating and optimizing tonabersat in standard glioblastoma therapy : a preclinical study. Kihara AH, editor. PLOS ONE. 2024;19(3).
IEEE
[1]
V. Zoteva et al., “Integrating and optimizing tonabersat in standard glioblastoma therapy : a preclinical study,” PLOS ONE, vol. 19, no. 3, 2024.
@article{01J03QBHN92EKFYAZXQ3BEJ74E,
  abstract     = {{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.}},
  articleno    = {{e0300552}},
  author       = {{Zoteva, Velislava and De Meulenaere, Valerie and Vanhove, Christian and Leybaert, Luc and Raedt, Robrecht and Pieters, Leen and Vral, Anne and Boterberg, Tom and Deblaere, Karel}},
  editor       = {{Kihara, Alexandre Hiroaki}},
  issn         = {{1932-6203}},
  journal      = {{PLOS ONE}},
  keywords     = {{GAP-JUNCTION PROTEIN,MONOCLONAL-ANTIBODIES,GLIOMA INVASION,CELL-LINES,RADIOTHERAPY,TEMOZOLOMIDE,FRAGMENT,CANCER}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{21}},
  title        = {{Integrating and optimizing tonabersat in standard glioblastoma therapy : a preclinical study}},
  url          = {{http://doi.org/10.1371/journal.pone.0300552}},
  volume       = {{19}},
  year         = {{2024}},
}
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