Tumour recurrence after treatment accounts for the vast majority of cancer deaths. With a particular focus on brain tumours, my research aims to understand how cancer cells become "invasive" - aquiring the ability to move into healthy tissue, where they can grow new, "secondary" tumours. It is my ultimate aim to translate this understanding into new therapeutic options to slow tumour spread and recurrence, ultimately improving outcomes for patients.

Glioblastoma, the most common and deadly adult brain cancer, recurs locally in over 90% of patients due to the infiltration of cancer cells beyond the limits of surgical resection. The resulting secondary tumours are typically unsuitable for reoperation and further care is often palliative. Therefore, invasive GBM cells that breach the tumour margin represent attractive targets for combination with standard of care prior to and following surgery. However, although spatial and single-cell ‘omics approaches have characterised invading cells in significant molecular detail, these approaches fail to describe mechanical forces such as traction and tension that are required for invasion. Additionally, how the cell-matrix adhesion proteins that control cell migration and invasion contribute to cancer cell phenotype and malignancy is not fully understood - especially in the case of rare or alternatively spliced proteins. Our incomplete understanding of these proteins and the forces that they generate is a significant impediment to progress in brain tumour therapy.

To address these challenges, my research asks three questions. First, how do changes to the transcriptional and epigenetic status of cancer cells result in the aquisition of an invasive phenotype? Second, how do cancer cells convert their repertoire of cell-matrix adhesion proteins into the biomechanical force required for invasion? And finally, how do rare or novel adhesion protein variants contribute to cancer cell malignancy? Together, these questions aim to address a key knowledge gap in glioblastoma that could hold significant therapeutic opportunity. Furthermore, I aim to expand this knowledge beyond the scope of glioblastoma in the future by exploring these topics in diffuse midline glioma: a childhood brain tumour with extremely limited therapeutic options.