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

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

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.

• Jezik: Angleški jezik
• Ključne besede: cellular physiology, cellular toxicology, in vitro toxicology, 3D culture, technical aspects, cell biology, cancer
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FRI - Fakulteta za računalništvo in informatiko; BF - Biotehniška fakulteta ; MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 19 str.
• Številčenje: Vol. 27, iss. 9, art. 110604
• PID: 20.500.12556/RUL-166746
• UDK: 576
• ISSN pri članku: 2589-0042
• DOI: 10.1016/j.isci.2024.110604
• COBISS.SI-ID: 205414147
• Datum objave v RUL: 23.01.2025

Gradivo je del revije

• Naslov: iScience
• Založnik: Elsevier
• ISSN: 2589-0042
• COBISS.SI-ID: 24098568

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: glioblastom, organoidi, monoterpeni, rak, onkologija, celična fiziologija, celična toksikologija, celična biologija, toksikologija in vitro