Drug repurposing and investigation of novel combinations for glioblastoma therapeutics using in vitro and zebrafish in vivo models

Limited Access
This item is unavailable until:
2024-07-16
Date
2024-01
Editor(s)
Advisor
Karakayalı, Özlen Konu
Supervisor
Co-Advisor
Co-Supervisor
Instructor
Source Title
Print ISSN
Electronic ISSN
Publisher
Bilkent University
Volume
Issue
Pages
Language
English
Journal Title
Journal ISSN
Volume Title
Series
Abstract

Glioblastoma is the most common and aggressive brain cancer type with the survival rate less than 2 years after diagnosis. Yet, potent drug treatments used in patients are limited and the field is in need of development of new potential drugs. In this study, repurposing of approved drugs alone or in combination and novel drugs are investigated in terms of inhibition of cell viability, glial fluorescent signals and their effects on behavior in zebrafish larval models. The main aim of this study was to test whether phenothiazines, trifluoperazine and a novel molecule 10, could be repurposed for glioblastoma treatment with lower dosages and more potency when combined with Sorafenib, an approved drug, in glioblastoma cell lines and zebrafish larvae. Those drug combinations were not found as toxic in the dosages studied while acted on glia cells in zebrafish transgenic larval models. Last but not least, behavior and stress response of the wild type and heterozygous mutant ache larvae in comparison with homozygous siblings were tested upon drug administration to assess genotype by drug interactions. Combination treatments exhibited higher efficacies suggesting phenothiazines with sorafenib could have potential in glioblastoma treatment. Genotype specific effects of individual and combination treatments on larval light-dark behavior, stress response and recovery exhibited potential for passage of blood brain barrier by the tested drugs. The established protocols for genotype and drug interactions could be applied to other kinases in combination with phenothiazines.

Course
Other identifiers
Book Title
Citation
Published Version (Please cite this version)