Interrogation of novel Glioblastoma Subtypes towards an improved Precision Medicine Approach for Brain Tumour Patients

Glioblastoma (GBM) is the most frequent and aggressive adult brain tumour. Sadly, 85% of patients die within two years, despite surgery and chemo/radiotherapy. Treatment resistance is related to cell types that make up the tumour (“tumour microenvironment” or “TME”). Specifically, the behaviour of TME cells such as blood vessel and immune cells often determines therapeutic response. We believe that studying the TME will provide information on which drugs would be best for specific patients, an approach known as ‘precision medicine’.

To do this, a reliable method of selecting the right patients for the drug of choice is required. In a previous project (www.gliotrain.eu), we analysed GBM tumours and used bioinformatics to group the tumours into three “subtypes” based on TME composition. Here, using tumour material from GBM patients we will investigate the underlying genetic differences between these TME subtypes. We will do this at the ‘tissue’ and ‘single-cell’ level. Next, we will merge all of the datasets to try and uncover TME subtype specific vulnerabilities and resistance mechanisms. Finally, we will develop preclinical models with tumours representing each subtype and will use these models to study ‘precision medicine’ treatment strategies. Specifically, we will choose drugs that should work in each subtype, based on ‘targets’ expressed by specific tumours. Importantly, we will test immunotherapy drugs, which have to date not been successful in GBM clinical trials.

Overall, our goal is to develop a new TME-based precision medicine approach, which will provide new treatments for GBM, which is a difficult-to-treat and largely fatal cancer. Following successful completion of this study and in collaboration with clinical colleagues at The National Centre for Neurosurgery, Beaumont Hospital Dublin, we aim to initiate Ireland’s first Phase 2 trial in GBM patients.
 

Award Date

01 July 2022

Award Value

€370,000.00

Principal Investigator

Professor Annette Byrne

Host Institution

Royal College of Surgeons in Ireland

Scheme

Investigator Led Projects