Official title: Systems approach to therapeutic combinations for glioblastoma: new targets and agents delivered and sequenced for synergy
Lead researcher: Professor Neil Carragher
Where: University of Edinburgh
Cost: We will fund £3million (total grant award £6.28million, with Cancer Research UK) over a five-year period
Research type: Adult, Glioblastoma (high grade), Academic
A multi-disciplinary collaboration, this research programme includes international experts in genomics, protein analysis, creation of pre-clinical models, and drug delivery.
Funded by us, through this grant, Professor Carragher will adopt a systematic approach to find new drug targets and new drug combinations to treat glioblastomas. In addition to discovering new combinations of drugs, they’ll continue their work by testing drug combinations already discovered by their team.
Identifying drug targets
The research team will search through various drug databases to identify molecules that could be useful in combination with the current standard of GBM treatment (temozolomide and radiotherapy).
They’ll then conduct phenotypic screens. This tests the way cells respond to drugs and analyses this through changes in the cells’ appearance. The team will also go further and use a technology called CRISPR-i to identify ways to prevent treatment resistance, helping improve survival rates.
Validating drug targets
Pre-clinical models will be used to determine which genes are involved in causing tumour development and growth, as well as testing which drugs will be effective in killing the tumour cells and preventing resistance to treatment.
Multiple tumour models will be used because no single model accurately represents everything that happens within all people. By evaluating the drug combinations in multiple models, the team will ensure that these drugs have the highest chance of success in people diagnosed.
Understanding how drugs work
Researchers will use various lab tests to help them understand the cell signalling pathways that the drugs activate. Cell signalling is a cascade of reactions that happen within a cell. These reactions help coordinate a cell’s activities such as growth and repair, and can be manipulated to stop tumour growth.
By understanding these signalling pathways, the researchers will have a better understanding of how these drugs are working and what causes resistance to treatment.
Optimising drug delivery
Delivering drugs to brain tumours is challenging due to the presence of the blood brain barrier – tightly packed cells that line the walls of the blood vessels in the brain. These cells allow only some substances such as water, oxygen and essential nutrients to pass through in order to protect the brain. However, it can have a negative affect when trying to treat a brain tumour as it will stop the treatment reaching the brain and, therefore, the tumour.
The team will build upon previous research to develop a chemical ‘courier’ to deliver the drug combinations, as they play a key role in crossing the blood brain barrier.
The prognoses for people diagnosed with a glioblastoma is dismal. Even with the current gold standard of care, which includes surgery, followed by radiotherapy and temozolomide, less than 5% of people with a glioblastoma survive for more than five years.
The poor prognoses can be attributed to what makes up the tumour (its composition), as glioblastomas are composed of different types of cells. This diverse composition results in the failure of chemotherapeutic and targeted treatments, as they tackle only one kind of cell within the tumour. Combination therapies would allow doctors to target multiple aspects of glioblastoma, allowing for more effective results.
This grant will allow researchers to suggest new combinations of therapies which have the greatest chance of being effective and well-tolerated in people. We hope that these new therapy combinations will signify a real step-change in the lives of people with a glioblastoma, improving quality of life and length of survival.
The treatment for people with a glioblastoma has not changed in a decade and there’s an urgent need for new treatments. This research programme aims to address this need and go one step further by determining combinations of drugs to help people diagnosed with a glioblastoma as well as identifying new ways to avoid treatment resistance.
This could make a real and positive difference to people being treated for a GBM, and their loved ones.
We’re looking forward to seeing the achievements of this group when the project starts.
If you have any questions about this, or any of our other research projects, please contact us on email@example.com
Research is the only way we will discover kinder, more effective treatments and, ultimately, stamp out brain tumours – for good! However, brain tumours are complex and research in to them takes a great deal of time and money.
Across the UK, over 100,000 families are facing the overwhelming diagnosis of a brain tumour and it is only through the generosity of people like you can we continue to help them.
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Professor Neil Carragher is the co-director of the Edinburgh Cancer Discovery Unit. He has strong links with the pharmaceutical industry and is focused on translational research.