Advancing Glioblastoma Therapy with 3D in Vitro Tumour Models

<p dir="ltr">Glioblastoma (GB) is a malignant brain astrocytoma of aggressive nature, which has limited treatment options and a very poor prognosis. This creates a strong demand for reliable preclinical models for the testing of new approaches. This study explores various aspects of the application of different types of 3D in vitro models of GB for advancing the treatment of this deadly tumour. Combination drug therapy presents a promising strategy to target different tumour mechanisms at the same time. My research specifically focuses on investigating the drug combination of an approved antifibrotic drug, Pirfenidone (PF), with the GB standard of care chemotherapy agent, Temozolomide (TMZ), in 3D spheroid GB models in comparison with the conventional 2D monolayer cell cultures. Next, I performed a proteomics study to explore the molecular mechanism of action of PF applied alone and in combination with TMZ in 2D in vitro models of GB. Additionally, the study quantitively evaluates the performance of four popular cell counting assays in scaffold-based 3D GB models, including Matrigel-based constructs and original tissue engineering constructs that include decellularized brain matrices. These experimental findings are placed in the context of the current GB modelling and pharmacological research via the peer-reviewed and published comprehensive literature review. This thesis contributes to a better understanding of the advantages and limitations of different 3D in vitro models of GB and provides the methodological workflows and research findings regarding the evaluation of combinational treatment approaches.</p>