Long-term three-dimensional glioblastoma cell culture model for drug response studies
2023
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2023 by the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт:
Introduction: Glioblastoma, although not the most common, is one of the deadliest human cancers.
Despite the implementation of the Stupp protocol in clinical practice, which prolongs patients’ survival
for only 2.5 months, there have been no significant advances in glioblastoma treatment. Therefore, it is
imperative to better understand the mechanisms behind glioblastoma behavior for more efficient treat-
ment in the future. Conventional two-dimensional cell cultures provide an affordable and easy-to-
perform in vitro system but fail to recapitulate glioblastoma’s complex tumor structures and
microenvironmental conditions, which often results in a lack of translation to clinical settings. In con-
trast, three-dimensional (3D) cancer models can advance the understanding of cancer biology and have
the potential to revolutionize the development of new drugs and predict their clinical efficacy.
Methods: We have developed a novel long-term 3D glioblastoma model with potential applications in
preclinical studies. Using alginate fibers, this model allows the cultivation of U87 glioblastoma cells for
extended periods, lasting up to 28 days, which corresponds to a clinically relevant treatment cycle.
Results: This model was used to validate hypothesized optimal temozolomide scheduling for glioblas-
tomas generated via mathematical modeling. The results indicated that increasing the time spacing be-
tween doses of TMZ may reduce toxicity, delay the development of drug resistance, and potentially
improve survival outcomes.
Conclusion: In conclusion, the establishment and utilization of advanced 3D glioblastoma models offer
significant opportunities to advance our understanding of glioblastoma biology and improve treatment
outcomes.
Кључне речи:
Glioblastoma; Temozolomide; 3D cancer model; drug resistanceФинансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
У:
- Dobrijević Z, editor. Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade ; 2023. p. 32. (Trends in Molecular Biology; Special Issue).