The Effect of Combination Treatment with Temozolomide, Tumor Treating Fields, and TAS-119 on Glioblastoma Cell Culture

Dr. med. Kseniia Novikova

AutorIn

Dr. med. Kseniia Novikova

Titel

The Effect of Combination Treatment with Temozolomide, Tumor Treating Fields, and TAS-119 on Glioblastoma Cell Culture

Zitierfähige Url:

https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-989767

Übersetzter Titel (DE)

Die Wirkung der Kombinationstherapie mit Temozolomid, Tumor Treating Fields und TAS-119 auf Glioblastom-Zellkulturen

Erstveröffentlichung

2025

Datum der Einreichung

20.02.2025

Datum der Verteidigung

22.07.2025

Abstract (EN)

Glioblastoma is the most common and the most aggressive primary brain malignancy. Despite intense research and several new therapeutic options established in the last decades, the prognosis remains poor. Introduction of temozolomide into clinical practice as part of radiochemotherapeutic approach improved 5-years overall survival from 1.9 % to 9.8 %. Later, the application of TTFields, a portable device for non-invasive delivery of alternating electric field to the tumor site, was approved for glioblastoma patients. Augmentation of the therapy with TTFields led to another breakthrough, increasing median overall survival from 15.6 months to 20.5 months. Since glioblastoma is incurable, the search for a compromise between life prolongation and the preservation of functionality and quality of life is crucial in both surgical and conservative therapies. The objective of this work was to investigate the effectiveness of Aurora Kinase A inhibitor TAS-119 as a potential therapeutic partner on glioblastoma cell cultures in vitro. In the cell Aurora Kinase A is crucial for proper formation of mitotic spindle. Aberrant expression of this enzyme has been found in multiple cancer types, including glioblastoma, making it an attractive target for antitumor therapy. TAS-119 is a novel inhibitor with high selectivity for Aurora Kinase A and milder side effect profile in comparison to the other experimental Aurora Kinase A inhibitors. This study compared standard therapy with temozolomide and TTFields to the combinations of these therapeutic options with TAS-119. Furthermore, the effectiveness of triple combination in comparison to the double combinations was investigated. The present work was performed with commercial glioblastoma cell line U87-MG and three primary cell cultures obtained from the patients of the University Hospital Carl Gustav Carus Dresden diagnosed with glioblastoma. To evaluate the response of the cell cultures to the therapies, flow cytometry, light microscopy, and confocal laser scanning microscopy were employed. The experiments revealed significant additive cytotoxic effect of the double combinations with TAS-119 in comparison to the corresponding monotherapies, which was not the case for standard combination of temozolomide and TTFields. Thus, combinations with TAS-119 were more effective than the standard therapy. Comparison of both double therapies with TAS-119 did not identify a distinctly better option. However, combination of TAS-119 with TTFields tumor can potentially lead to less side effects for the patients than combination with temozolomide. Triple combination treatment was not more effective than the most effective double treatment for each cell line. These findings provide strong preclinical evidence supporting the potential of TAS-119 as part of a combination treatment for glioblastoma. Moving forward, further in vivo studies and eventually clinical trials will be essential to assess the therapeutic benefits and safety profile of TAS-119 in patients.

Freie Schlagwörter (DE)

Glioblastom, Aurora Kinase A, Temozolomid

Freie Schlagwörter (EN)

glioblastoma, TTFields, Tumor Treating Fields, TAS-119, AURKA, Aurora kinase A, temozolomide,

Klassifikation (DDC)

610

Klassifikation (RVK)

XH 8554

GutachterIn