Completed Cancer Brain & Nervous System

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

Funder MRC (part of UKRI)
Recipient organisation University of Glasgow
Funding £1.3M
Period Sept 2010 — Jun 2015

In plain English

AI plain-English summary

Brain tumour patients currently survive an average of just one year, and most tumours resist treatment from the start. This project aims to break that resistance by targeting the DNA repair machinery inside tumour cells. The problem is that radiotherapy and chemotherapy kill cancer cells by damaging their DNA, but many glioblastoma cells have ways to fix that damage and survive. The researchers have already shown that drugs called PARP inhibitors can block one of those repair pathways. Now they need to find out which patients will actually benefit from these drugs, and whether the drugs can also kill the stem-like cells that often cause tumours to regrow. If PARP inhibitors fail, the team will test other drugs that alter how cells respond to radiation. They are also developing a new approach for a particularly chemotherapy-resistant type of brain tumour, by reducing levels of a protein called MGMT that normally protects tumour cells. If this succeeds, the immediate impact is straightforward: longer survival for patients with a devastating diagnosis, without increasing damage to healthy brain tissue. The work is applied and patient-focused, with a clinical trial already planned.

View original technical description
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.

View the original record at the funder ↗

Researchers

Anthony Chalmers (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Evaluating the therapeutic potential of PARG inhibition in glioblastoma and further elucidating the mechanism(s) of action
PARADIGM: Olaparib And Radiotherapy In newly­diagnosed Glioblastoma
Investigating the role of epigenetic remodelling in glioblastoma in response to therapy
Investigating alternative modes of radiotherapy and the combination with DNA repair inhibitors in enhancing the treatment of glioblastoma
PARADIGM OlaPArib And RADiotherapy In newly-diagnosed GlioblastoMa:

Original classification

Fellowship

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.