A living biobank of post-surgical residual glioblastoma to replace animal studies

Animals in research generally do not receive the full spectrum of therapy that is standard-of-
care for patients, since surgical resection of tumours in rodent models is technically challenging
and unproven. Therefore, it is unclear whether survival gains in animal models reflect treatment
response within the core mass of the tumour, or the highly infiltrative margin. This is clinically
relevant, as in patients receiving standard treatment, only the infiltrative residual cells left behind
after surgery are responsible for disease progression. Consequently, we aim to establish a 3-
dimensional living biobank of glioblastoma which reflects the spectrum of resected and residual
disease in human patients, and demonstrate its utility as a highly-characterised, efficient and
clinically relevant alternative to animal studies.
Objectives:
1. Generate and characterise 15-20 (4 generated at present) paired GSC lines from the tumour
core and adjacent infiltrated brain of surgical specimens to comprehensively model resected and
residual disease, respectively (in addition to 15-20 further GSC lines where only resected
disease is available).
- This objective will incorporate comparison of response to conventional treatment in the living
biobank & corresponding patients to establish how well these models predict therapeutic
response in human patients.
2. Complete detailed functional comparison of cellular responses to IR and temozolomide (TMZ)
chemotherapy and contrast the associated transcriptomic landscapes between resected and
residual disease.
3. Provide proof-of-principle data that the living biobank can be used to identify new therapeutic
combinations which effectively target post-surgical residual disease - small molecules which
target the DDR will be used as an example since current patient treatment is based on DNA damaging agents (chemo- & radiotherapy).