Adopting ClonoScreen-3D, a high-performance 3D drug-radiation screening platform for CRISPR campaigns towards the identification of novel targets for radiosensitisation in glioblastoma

In collaboration with the Milner Therapeutics Institute, the aim of this project is to apply a 3D cell culture model, developed through an NC3Rs project grant, to investigate radiation-drug therapy combination and replace mice in these studies.

Glioblastoma tumours initially respond to radiotherapy but the presence of radiation resistant cells, termed glioma-like cells (GSCs), mean tumours reoccur, which can lead to patient death. Research is ongoing to identify new therapeutic targets to increase the effectiveness of radiotherapy. Professor Anthony Chalmers and Dr Natividad Gomez-Roman previously developed “ClonoScreen3D” using patient-derived GSCs that more closely resembles tumours growing in patients than 2D models of glioblastoma. The model more accurately predicts patient responses to agents than other preclinical models, both in vitro and in vivo, and can replace the use of intracranial xenograft mouse models where glioblastoma cells are implanted into the brain. Through the collaboration with the Milner Therapeutics Institute, the utility of the assay will be demonstrated by investigating whether specific genetic alterations in GSCs lead to radiotherapy resistance.