Modelling the biology of glioblastoma

Programme stream(s): Cancer discovery / underpinning research , Treatment
Programme session type(s): Bench to bedside

Chair: Simona Parrinello, University College London, UK
Presenter: Antonio Garcia-Trinidad, Astrazeneca, UK
Presenter: Kathreena Kurian, University of Bristol, UK
Speaker: Anthony Chalmers, University of Glasgow, UK
Speaker: Peter Dirks, Sick Kids, Canada
Speaker: Steve Pollard, University of Edinburgh, UK

16:35-18:35

Room: Boisdale

Glioblastoma (GBM) is the most common and malignant type of brain tumour, characterized by high recurrence and short survival. The pervasive cellular and molecular heterogeneity of GBM and insufficient understanding of its biology remain key clinical challenges. Preclinical models that accurately recapitulate GBM complexity are therefore essential for increasing understanding of disease mechanisms and developing improved therapies. This session will focus on recent advances in GBM modelling and on how these models are providing key insights into disease biology and innovative treatment strategies. Topics covered will include genomic drivers, mechanisms of cancer stem cell quiescence, self-renewal and maintenance, and invasion.

Pre-clinical models of glioblastoma that enable more accurate evaluation of new treatment combinations
Speaker: Anthony Chalmers
Affiliation: Glasgow Centre for Cancer Research

Abstract:

To date, molecular targeted agents have failed to improve outcomes for glioblastoma patients, despite promising pre-clinical data. The discrepancy between pre-clinical and clinical effects may be at least partly explained by the widespread use of conventional 2-dimensional cell culture and xenograft models derived from established cell lines, which fail to recapitulate key features of the human disease. We have developed a novel 3-dimensional cell culture system in which effects of radiotherapy-drug combinations differ from 2D systems and replicate outcomes of clinical trials. The model will be described along with illustrative data.For in vivo testing of promising combinations, intracranial injection of primary GBM cells that have been cultured to enrich the stem-like population generates orthotopic xenografts that recapitulate key histopathological features of GBM and can be used for pharmacokinetic, pharmacodynamic and efficacy studies of promising therapeutic combinations. These models are suitable for functional imaging studies and image guided irradiation protocols.