Past & Ongoing projects
Please find below a description of some of the ongoing projects within the Consortium:
COLOSSUS is a 5-year EU-funded Horizon 2020 project which began in January 2018 that aims to provide new & more effective ways to classify patients with a specific subtype of metastatic mCRC)), thus facilitating the development of new treatment options. Colorectal cancer is the third most common cancer in Europe, and approximately 50-55 % involve RAS mutations. Standard treatment for this subtype of colorectal cancer is based on 5-fluoruracil based chemotherapy +/-bevacizumab, but other treatment options are limited when patients develop resistance. COLOSSUS aims to improve predictions of treatment outcomes in MSS RAS mt mCRC patients, so that the right patients can be given the right treatments at the right time.
COLOSSUS is coordinated by EurOPDX member Prof Annette Byrne at the Royal College of Surgeons, Ireland, and also involves EurOPDX members from the University of Torino, Italy.
Glioblastoma (GBM), an aggressive and devastating form of brain tumour, is the focus of the 4-year project named GLIOTRAIN. As part of the EU Horizon 2020 Marie Sklodowska-Curie Innovative Training Network (ITN) initiative, the 4-year project which began in September 2017 will address the urgent need to identify new treatments for GBM, whilst also aiming to unravel disease resistance mechanisms through state-of-the-art genomics and systems medicine approaches. Taking a multi-pronged approach, GLIOTRAIN will foster the next generation of young scientists, supporting 15 PhD projects in areas including medical oncology, computational biology, and immunotherapy. This multi-sectoral industry-academia collaboration is co-ordinated by EurOPDX member Prof. Annette Byrne of the Royal College of Surgeons, Ireland (RCSI), and also includes EurOPDX member Prof. Simone Niclou from the Luxembourg Institute of Health (LIH), and will employ advanced PDX models of GBM in its research.
Project ColoForetell, funded by Science Foundation Ireland, aims to establish a state-of-the-art mCRC PDX discovery platform to enable the systematic interrogation of predictive -omic and imaging markers of intrinsic resistance. The effect of Regorafenib in a cohort of metastatic mCRC PDX models will be characterized using imaging and immunohistochemistry. An integrated whole exome sequencing /Reverse Phase Protein Array strategy will identify putative biomarker signatures & interrogate cellular signaling pathways using statistics and systems pathway analyses. Functional Magnetic Resonance Imaging will be assessed in novel orthotopic PDX models as a possible predictive imaging response marker. ColoForetell’s primary goal is the discovery & verification of predictive pharmaco- 'omic & imaging biomarker methods for Regorafenib.
ColoForetell is coordinated by EurOPDX member Prof. Annette Byrne at the Royal College of Surgeons, Ireland, and also involves EurOPDX member, Prof. Livio Trusolino from the University of Torino, Italy.
Breast Cancer Pharmacogenomics.
A pipeline for the performance of high-throughput single and combination drug screening assays in a feasible and cost-effective manner has been developed by EurOPDX members Dr. Alejandra Bruna and Prof. Carlos Caldas of the CRUK Cambridge Institute (UK). This pipeline combines in vivo maintenance of human-derived samples of breast cancer, as low passaged PDXs, with ex vivo short-term cultures (PDX cells or PDCs), as described in the Cell article: Bruna et al. 2016. This PDX_PDC integrated platform has been comprehensively characterized and been shown to closely recapitulate patient-specific treatment and rationally predicted targeted treatment responses.
The biobank used in the study is one of the largest in the world in an academic setting, and is being continually expanded. The biobank comprises of models from CRUK-CI as well as models from other EurOPDX consortium members; Institut Curie (France), the Vall d’Hebron Institute of Oncology (Spain), and the Netherlands Cancer Institute (The Netherlands). The initiative represents the first biobank of EurOPDX models with extensive molecular and drug response annotation that can be easily browsed in a public web portal developed in Cambridge, at https://caldaslab.cruk.cam.ac.uk/bcape/.
The models in this biobank will be made available for free Transnational Access (TA) as part of the EurOPDX Research Infrastructure project – www.europdx.eu/europdxri-ta, and will be visible on the newly developed EurOPDX Data Portal in time for the 2nd call for access (from September 2019). The biobanking standards established by CRUK-CI for this project now inform the biobanking procedures of the EurOPDX Research Infrastructure distributed biobank.