Funding

In addition to tumour cells, the glioblastoma (GBM) tumour microenvironment (TME) consists of many non-cancer cells, which exist in several niches and exhibit varying levels of interaction. We recently established a novel molecular subtyping approach based on TME composition and published our data this year in the leading journal Annals of Oncology. In summary, tumours were classified as TMELow (25%), TMEMedium(Med) (38%), or TMEHigh (37%). Molecular analyses identified mutations and uniquely altered biological pathways across subtypes. Please see our Flyer (https://www.glioresolve.eu/s/GLIORESOLVE-Flyer_FINAL1.pdf) which explains this work in lay language. Following re-analysis of data available from clinical trials, it is apparent that immunotherapies may be effective in TMEHigh patients but less effective in the TMELow and TMEMed patients. Here, we focus on studying novel TMELow subtype-specific treatments. Specifically, we will investigate whether TMELow tumours can be ‘primed’ to become more vulnerable to immunotherapies. We will employ faithful pre-clinical models (representing the TMELow subtype) to establish treatment toxicity and efficacy. Tissue collected during these studies will undergo cytokine spatial proteomic analyses to mechanistically assess novel treatment response patterns and resistance mechanisms. Project outputs will include an extended characterization of the TMELow GBM subtype, and will provide new approaches to sensitise TMELow patients to immunotherapeutic interventions. Our overall objective is to generate sufficient data to support initiation of a Phase 2 trial at Beaumont hospital.

Funder: Beaumont Hospital Cancer Research Trust

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 GLIOTRAIN (https://cordis.europa.eu/project/id/766069), we analysed GBM tumours  and used bioinformatics to group the tumours into three “subtypes” based on TME composition. In this project, 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.

Funder: HRB

Glioblastoma (GBM) is the most frequent, aggressive and lethal brain tumour. It has a universally fatal prognosis with 85% of patients dying within two years. New treatment options and precision medicine therapies are required. This must be achieved by multi-sectoral industry-academia collaborations in newly emerging, innovative research disciplines. Glioresolve is an EU Horizon funded Doctoral Networks project which follows on from the recently completed Gliotrain. The Glioresolve consortium brings together leading European academics, clinicians, private sector and not-for-profit partners, and incorporates disruptive research methods including multiomics, ex-vivo ‘tumour-on-a-chip’ assay development, computational modelling and systems biology. Overall Glioresolve provides a comprehensive translational research strategy that goes significantly beyond the current state-of-the-art in neuro-oncology, to establish a new tumour micro-environment (TME)-targeting precision medicine platform for GBM.

Funder: EU Horizon Europe

Website coming soon

This HEA North-South Research funded project is looking at the development and validation of a CT-based radiomics signature for early detection of colorectal cancer liver metastasis and post-treatment disease recurrence

Funder: HEA

The National Preclinical Imaging Centre (NPIC), which is the first of its kind in Ireland, has been established and co-funded by RCSI University of Medicine and Health Sciences, University College Dublin (UCD), and CÚRAM, the SFI Research Centre for Medical Devices, based at National University of Ireland Galway (NUI Galway).

The Centre’s imaging infrastructure supports the development of new therapeutics and diagnostics in human disease areas including cancer, neurology, dementia, psychiatry, cardiology, medical devices, diabetes, tissue engineering, nanomedicine and inflammatory disease. 

The Centre provides a national pre-clinical imaging resource open to all academic, industry and not-for-profit researchers, and has locations in Dublin (RCSI, UCD) and Galway (NUI Galway). NPIC establishes a national pre-clinical magnetic resonance (MR) facility, a national high-field preclinical MR / chemical imaging platform and incorporates a high-resolution micro-computed tomography (CT) and Optical Imaging laboratory.

Funder: SFI

www.NPIC.ie

ResearchGate page

Colorectal cancer (CRC) is the third most common cancer in Europe. It is estimated that 50-55% harbour RAS mutations. Current treatment for RAS mutant(mt) metastatic(m) CRC is based on 5-fluoruracil based chemotherapy +/- bevacizumab. There are limited treatment options once cancers become resistant. Targeted treatment of microsatellite stable (MSS) RAS mt disease is difficult and has not evolved significantly in recent years. COLOSSUS looks to deliver novel concepts for disease-mechanism based patient stratification in MSS RAS mt mCRC to address the need for stratified or personalised therapies. The consortium aims to integrate multidimensional and longitudinal omics data to identify new MSS RAS mt specific subtypes. Systems biomedicine, network analysis and computational modelling are utilised to identify new actionable pathways, biomarkers and targets across subtypes. These targets are then interrogated in pre-clinical patient derived xenograft studies. Newly described MSS RAS mt classifiers are then validated within the COLOSSUS trial. These results are then used by our SME partners to develop clinically relevant and commercially viable assays for outcome prediction and stratification of MSS RAS mt patients based on novel classifiers. This work also includes patient associations through which perform public and and patient involvment (PPI) events are hosted.

Funder: Horizon 2020 

www.colossusproject.eu

Colorectal cancer (CRC) is the third most common cancer in Europe with an estimated 420,000 new cases diagnosed and 230,000 related deaths anticipated in 2018. CRC is the 2nd most common and 2nd most fatal cancer in Ireland. Currently standard chemotherapy (FOLFOX) and bevacizumab [(BVZ); avastin] a drug which inhibits tumour blood vessel formation are standard of care treatments for CRC patients. However, only a subpopulation of patients benefit from treatment and for the majority, their tumors regrow and spread to distant organs like the liver and lungs. Furthermore, avastin is a costly drug and has some serious side effects. Recently we have discovered that chromosomal instability (where whole human chromosomes or parts of chromosomes are duplicated or deleted) may predict which patients will receive most benefit to avastin. By predicting the patients that would not benefit from avastin, individuals could be spared the side effects of this particular drug therapy, and are more likely to receive optimal treatment with a minimum of delay, while reducing cost of care. Based on these findings, we now wish to develop a laboratory test, which can be used in patients to detect these chromosomal rearrangements in DNA that is found freely in blood. This test will be based on a simple blood test making it easy to screen patients and predict whom will likely respond to avastin treatment    

Funder: HRB

Colorectal cancer is often treated with chemotherapy and Avastin. However, Avastin only benefits a sub-group of patients. Recently, we discovered that chromosomal instability (chromosomes duplicated or deleted) may represent a “biomarker’ to predict which patients might respond. To understand how our biomarker works, we must now unravel the underpinning biological mechanisms. We will do this by analysing genetic data from patients and utilising preclinical models, medical imaging and tumour protein analyses. Overall, this will help us take our new biomarker into the clinic, with an overall goal to improve colorectal cancer patient care and outcomes

Funder: SFI

Lead PI: Prof Mark Cunningham - TCD

Seizures are a frequent symptom for patients with brain tumours and are poorly controlled. These seizures are due to an increased level of a chemical messenger, or neurotransmitter, around the tumour. Neurotransmitters such as glutamate allow brain cells to talk to one another. Glutamate does this by exciting brain cells. Excessive glutamate overexcites brain cells around the tumour causing seizures. We will explore the potential to use a gene therapy approach to deliver a protein to the brain that in the presence of excessive glutamate will silence abnormal brain cells to stop seizures.

Funder: SFI

We would like to express our gratitude to all the funding agencies who have supported our work, including Science foundation Ireland, the Health Research Board, the Irish Cancer Society, Enterprise Ireland, the Higher Education Authority, Beaumont Hospital Foundation and the EU

Glioresolve

Radcol

NPIC

COLOSSUS

HRB Liquid Biopsy

SFi chromosomal instability

SFI BTRE Gene Therapy