Professor Neil Carragher’s lab in Edinburgh focuses on finding new treatments for glioblastoma. This project is in collaboration with international experts at Massachusetts Institute of Technology (MIT) and the University of Oxford – harnessing the skills and knowledge of some of the very best researchers in the field.
The project takes a novel approach to finding treatments for glioblastoma by testing huge numbers of potential drug compounds on cells from different types of glioblastoma cells.
Glioblastoma cells vary and this is caused by the changes in the tumour DNA. This is why glioblastomas respond differently to different treatments, making them difficult to treat in people facing this devastating diagnosis.
By trying to find drugs that work against the different types of glioblastoma, Professor Carragher and his team of researchers hope to find different drugs or drug combinations to better treat this disease, regardless of the DNA changes in the tumour cells.
The project has four main objectives:
- Find potential drugs and targets for these drugs
- Check that these drugs are good contenders as future treatments
- Understand how these drugs work
- Find the best ways to deliver these drugs to patients
1. Finding potential drugs and targets for these drugs
Screening for new drugs
To date, more than 3,000 drugs have been screened against six different glioblastoma cells cell taken from people diagnosed with this type of brain tumour. Different doses of each of these drugs have been tested to find out which worked best against the tumour cells. A number of these have shown potential as treatments and will be taken to the next stages of the research.
This work is being carried out at the University of Edinburgh as part of the Drug Discovery Research programme. This programme allows a huge number of potential drugs to be tested quickly. Some of the drugs are new and some are approved for other diseases which may be able to be repurposed to treat brain tumours.
Understanding the changes to DNA in tumour cells
Alongside the drug screening, researchers have investigated how glioblastoma cells survive and become resistant to treatment. They have identified two enzymes involved in cancer cells’ survival. The team have started to investigate different combinations of drugs that target these two enzymes.
Professor Carragher’s team have also identified a number of different genes that could be involved in treatment resistance. These will be investigated further to find which ones are most important and how we could combat them with new drugs.
2. Check that these drugs and targets are good contenders as future treatments
The drugs that have been identified as potential treatments for glioblastoma are further tested in a number of laboratory models newly developed for this research. This will help to determine which drugs or combinations of drugs will be most effective at killing tumour cells and preventing resistance to treatment.
3. Understanding how these drugs work
The researchers use computer modelling to help them understand how the drugs affect glioblastoma cells as it is important to understand how drugs are slowing or preventing tumour growth.
The team also aim to find combinations of drugs that work well together. This could mean that drugs which have already been developed may have a greater impact when they are used in combination with other drugs.
4. Find the best ways to deliver these drugs to patients
Delivering drugs to brain tumours is challenging due to the presence of the blood-brain barrier. Researchers are developing nanoparticles, which act as “chemical couriers”, to cross the blood-brain barrier and deliver the drugs to the site of the tumour. Their future work is focused on loading these nanoparticles with single drugs and drug combinations, and analysing how efficiently they can transport the drugs to the site of the tumour and measuring the effects of these drugs on the tumour in preclinical models.
This work has been made possible as a result of money raised by The Emily Morris Fund.