Overcoming treatment resistance in glioblastoma multiforme by tumour specific inhibition of DNA repair.

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At the moment, most malignant brain tumours are resistant to treatment and patients live for an average of only one year. The aim of our research is to improve life expectancy for these patients by increasing the effects of radiotherapy and chemotherapy on the tumours without increasing damage to healthy tissues. Our previous work with drugs called PARP inhibitors has been promising, and we have planned a clinical trial to see if patients benefit. One aim of this project is to identify which patients benefit from PARP inhibitors, and to understand why. We will also investigate whether PARP inhibitors increase the ability of radiotherapy to eradicate the cells that are probably responsible for most cases of tumour recurrence. If PARP inhibitors are not effective we will test other drugs that affect the way cells respond to radiotherapy. Finally, we will investigate a possible new treatment for a type of brain tumour that is extremely resistant to chemotherapy. The new treatment appears to reduce levels of a protein called MGMT which otherwise protects tumour cells from chemotherapy. We need to show that the new drug increases killing of brain tumour cells without causing extra damage to healthy tissues.