Investigating alternative modes of radiotherapy and the combination with DNA repair inhibitors in enhancing the treatment of glioblastoma
Background
Glioblastoma (GBM) is the most common brain cancer in adults, but where survival rates (<12 months) remain extremely poor largely due to the inherent resistance of the tumour to therapies, including conventional (X-ray) radiotherapy. However, the emergence of precision targeted proton beam therapy (PBT) and boron neutron capture therapy (BNCT) offer alternative modes of radiotherapy that can significantly reduce the side effects observed with conventional radiotherapy, whilst also being more effective in tumour cell killing. Despite this, there are still biological and clinical uncertainties with PBT and BNCT, requiring further research to be conducted in appropriate preclinical GBM models. Furthermore, the identification of specific drugs (such as those targeting the DNA damage response) that can be utilised to enhance the biological effect of PBT and BNCT, is currently unclear. This research is essential in deriving the optimal radiotherapy strategy that can be used in the clinic for the benefit of GBM patients.
Objectives
This exciting DTP studentship will develop novel radiation biology research investigating the impact of PBT and BNCT, versus X-rays, in overcoming the radioresistance of GBM. We will also explore the effect of targeted DNA repair inhibitors (collaboration with AstraZeneca) in the radiosensitisation of GBM models in response to the different radiotherapy types. This will be delivered through the unique radiotherapy facilities (MC-40 cyclotron and high flux accelerator-driven neutron facility) available in Birmingham, in combination with GBM cell lines, 3D spheroids/patient-derived organoids and a chick embryo tumour model.
Apply by midday (GMT) Friday 12 January 2024