Recipient organisationNIHR Sheffield Biomedical Research Centre
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Mar 2027
In plain English
AI plain-English summary
Glioblastoma tumours use the brain’s own support cells to help them resist treatment and spread, and this project will examine whether ageing makes those support cells more dangerous. This matters because glioblastoma is the most lethal brain cancer, with a median survival of just 10–15 months that has not improved in decades. The disease primarily strikes older adults, yet this group is routinely excluded from clinical trials. Tumour recurrence is driven by glioblastoma stem cells that migrate beyond the surgical margin, protected by tumour-associated astrocytes. The researchers have a rare resource: large en bloc surgical resections that include the brain tissue where recurrence happens, allowing them to study how astrocytes and stem cells interact in older patients. If this work succeeds, it could reveal why older patients face worse outcomes and identify astrocyte-driven mechanisms of treatment resistance. That knowledge might eventually lead to therapies that block the tumour’s escape routes, improving survival for the growing population of older glioblastoma patients. The research is fundamental—it first needs to establish how ageing alters astrocyte behaviour in the tumour microenvironment before any clinical application becomes possible.
View original technical description
Glioblastoma (GBM) is the most aggressive and lethal form of brain cancer. Despite intensive treatments that combine surgery, chemotherapy, and radiotherapy, GBM invariably recurs, leaving patients with a median survival of 10-15 months. This prognosis has remained largely unchanged for decades, despite the significant strides made in treating many other cancers. GBM primarily affects older adults. Alarmingly, this demographic is often excluded from clinical trials, limiting our understanding of treatment efficacy in this vulnerable group. Meta-analysis of trials including older patients show they face significantly worse outcomes regardless of treatment, which is a stark contrast to other cancer types. As the population ages, the incidence of primary GBM is rising, intensifying the need for new therapeutic strategies tailored to older patients. Current GBM treatments are limited in addressing the root causes of recurrence. The disease often re-emerges beyond the margins of surgical resection due to glioblastoma stem cells (GSCs), present at the tumour core and surrounding brain. These GSCs exhibit resistance to chemotherapy and radiotherapy, driven in part by the tumor microenvironment (TME). However, the area where disease reoccurs is not routinely available to researchers. Our group utilises large, en bloc resections, where for patient and tumour specific regions, large areas of the brain are needed to be removed along with the tumour. This presents a rare opportunity to study how the GSC migrate into the brain, where they usually reside beyond the resection margin. Within the TME, tumor-associated astrocytes (TAA) play a critical role by enabling the migration of treatment-resistant GSCs deeper into the brain. Interestingly, similar patterns of astrocyte activation are seen in ageing astrocytes, raising the question of whether these age-related changes exacerbate resistance in GBM. This project focuses on the interaction between astrocytes and GSCs in older adults to unravel the mechanisms driving treatment resistance.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know