Patient-derived tumor organoids mimic treatment-induced DNA damage response in glioblastoma

Majc, Bernarda (author), Habič, Anamarija (author), Malavolta, Marta (author), Vittori, Miloš (author), Porčnik, Andrej (author), Bošnjak, Roman (author), Mlakar, Jernej (author), Matjašič, Alenka (author), Zupan, Andrej (author), Skoblar Vidmar, Marija (author), Lah Turnšek, Tamara (author), Sadikov, Aleksander (author), Breznik, Barbara (author), Novak, Metka (author)

Glioblastoma (GB) is the most common primary malignant brain tumor, characterized by resistance to therapy. Despite aggressive treatment options, GB remains an incurable disease. Invasiveness and heterogeneity are key GB features that cannot be studied in preclinical in vitro models. In this study, we investigated the effects of standard therapy using patient-derived GB organoids (GBOs). GBOs reflect the complexity and heterogeneity of the original tumor tissue. No significant effect on GBO viability or invasion was observed after irradiation and temozolomide treatment. E3 ubiquitin-protein ligase (MDM2), cyclin-dependent kinase inhibitor 1A (CDKN1A), and the serine/threonine kinases ATM and ATR were upregulated at the gene and protein levels after treatment. Our results show that the p53 pathway and DNA-damage response mechanisms were triggered, suggesting that GBOs recapitulate GB therapy resistance. GBOs thus provide a highly efficient platform to assess the specific responses of GB patients to therapy and to further explore therapy resistance.

• Language: English
• Keywords: cellular physiology, cellular toxicology, in vitro toxicology, 3D culture, technical aspects, cell biology, cancer
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FRI - Faculty of Computer and Information Science ; BF - Biotechnical Faculty; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 19 str.
• Numbering: Vol. 27, iss. 9, art. 110604
• PID: 20.500.12556/RUL-166746
• UDC: 576
• ISSN on article: 2589-0042
• DOI: 10.1016/j.isci.2024.110604
• COBISS.SI-ID: 205414147
• Publication date in RUL: 23.01.2025

Record is a part of a journal

• Title: iScience
• Publisher: Elsevier
• ISSN: 2589-0042
• COBISS.SI-ID: 24098568

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: glioblastom, organoidi, monoterpeni, rak, onkologija, celična fiziologija, celična toksikologija, celična biologija, toksikologija in vitro