Curing Brain Cancer One Cell at a Time: Spatial, Single Cell Transcriptomic Analysis of Glioblastoma Brain Tumour Treatment Response

Glioblastoma (GBM) is the most aggressive form of adult brain cancer, with poor prognoses despite surgery and chemoradiation. One of the key challenges is that residual GBM cells often become resistant to treatment, causing the tumour to regrow. Dr. Lucy Stead (primary supervisor) has recently identified that GBM recurrent tumours fall into two subgroups based on how their tumours adapt and evade the current standard of care. This insight has the potential to guide more targeted, personalised treatments that could improve outcomes. However, to do that, we we must fully understand the mechanisms behind these distinct treatment responses.

GBM tumours are highly heterogeneous, in that, any one tumour can be made up of many different types of cancer cells. These cells are highly plastic, meaning they can change their behaviour in response to treatment, and this behaviour is influenced by the surrounding tumour microenvironment (TME). Preliminary data from bulk RNA sequencing already suggests that these cancer and TME cell types are present in varying proportions across the two GBM subgroups and respond differently to treatment. However, this initial data lacks the spatial and cellular resolution necessary to pinpoint therapeutic targets.

This project will address this by utilising cutting-edge spatial transcriptomics, which allow us to map gene expression across individual cells and specific regions of GBM tumours, before and after treatment. Dr. Rachel Queen (second supervisor) is an expert in evaluating these specific datasets, having developed and released software packages for their analysis. By applying these advanced techniques to a unique collection of paired pre- and post-treatment GBM samples, we aim to further characterise the differences between the subgroups and identify key drivers of treatment resistance. This dataset represents the largest collection of such samples in the UK, providing a rare and valuable resource for understanding cancer cell plasticity at an unprecedented level of detail.