Breast cancer represents a leading cause of cancer death in women and a major socio-economic issue. With currently available methods, early diagnosis frequently fails. Moreover, beyond mere detection, there is an ever-increasing need for improved non-invasive characterisation of cancer. Targeted therapies require an in-depth analysis of cancer to select and guide appropriate treatment. Both, PET and MRI can provide molecular and functional information that may be of pivotal importance for tailoring therapy. However, current whole-body PET/MRI systems lack the necessary sensitivity and resolution for this task. HYPMED addresses this by engineering an innovative imaging tool. HYPMED will integrate an innovative fully-digital MRI-transparent PET-detector into a novel multi-channel PET-transparent MRI surface coil. The PET-RF insert will allow unprecedented imaging of breast cancer with high-resolution/ultra-high sensitivity PET, combined with high-level structural and functional MRI, and allow minimal-invasive MR- and PET-guided targeted biopsy. Moreover with such PET-RF inserts, every regular clinical MR-system can, upon demand, be turned into a hybrid system. We will evaluate the impact of this technology on breast cancer diagnosis, prediction, and monitoring/assessment of treatment response by a carefully designed clinical study that employs established and novel PET tracers in 250 patients. Imaging data will be correlated with established and novel molecular biomarkers; results will be compared to those obtained from whole-body PET/MRI and PET/CT. A multidisciplinary consortium of clinical scientists, 3 SMEs and an industry partner will pave the way for commercialization of HYPMED products for advanced clinical decision making in cancer patients. Once HYPMED is successful, we will expand this approach to other applications such as prostate cancer or cardiac hybrid imaging, and thus introduce a paradigm shift in the field of PET/MR hybrid imaging as a whole.

Pharmacogenomics is the study of genetic variability affecting an individual’s response to a drug. Its use allows personalized medicine and reduction in ‘trial and error’ prescribing leading to more efficacious, safer and cost-effective drug therapy. The U-PGx consortium will investigate a pre-emptive genotyping approach (that is: multiple pharmacogenomic variants are collected prospectively and embedded into the patients’ electronic record) of a panel of important pharmacogenomic variants as a new model of personalised medicine. To meet this goal we combine existing pharmacogenomics guidelines and novel health IT solutions. Implementation will be conducted at a large scale in seven existing European health care environments and accounts for the diversity in health system organisations and settings. Feasibility, health outcome and cost-effectiveness will be investigated. We will formulate European strategies for improving clinical implementation of pharmacogenomics based on the findings of this project.

Breast cancer (BC) is the most diagnosed cancer worldwide, and despite treatment availability, the disease remains challenging to treat, causing substantial adverse side effects and fatalities globally. The lack of efficacy and inaccessibility of standard care supports this demand for better treatments. This is demonstrated by resection surgery and current (neo)adjuvant therapies such as chemotherapy exhibiting inadequacies resulting in 30% of BC patients having metastases. These percentages are even higher in low human index regions due to inaccessibility, cost and growing populations. Adoptive cell therapy (ACT), such as CAR-T, is a category of emerging immunotherapies expected to impact oncology by transferring engineered immune cells into a patient to eliminate cancer cells. However, these treatments are currently ineffective in BC and costly. END-BC will complement research into B cells to produce an ACT that improves treatment efficacy against breast cancer while reducing side effects and costs from effective therapy. Our research developed novel biomaterial to overcome significant obstacles to successfully enhance B cell functions against cancer using a low-cost method. In END-BC, we will research the commercial and technical feasibility of tailoring the B cell ACT with biomaterials to determine its potential to treat BC.

TransQST will develop a Quantitative Systems Toxicology (QST) approach, employing pre-existing data where possible, in order to yield new mechanistic insight into drug-induced toxicity. A central tenet of our programme will be to ensure the human physiological and pharmacological relevance of any test system that has been (or will be) used for generating the input data for modelling. By adopting this approach, we will be able to accurately interpret what happens when test systems are perturbed by drug exposure, and ensure translatability of modelling tools. Mechanistic translational biomarkers are a core aspect of our approach and will be applied in parallel with evidence for understanding how to develop, model and apply such biomarkers in a QST setting. The project is structured in 8 work packages to provide the following outcomes: curate the best available experimental data suitable for modelling adverse drug reactions; provide fit-for-purpose QST models that will address key toxicity measures for liver, kidney, heart and GI-tract; provide quantitative risk assessment for off-target toxicity in man based on in vitro and in vivo models; provide a quantitative mechanistic read-across from species (in vivo and in vitro) currently used for the toxicological evaluation of a new drug; provide definition and applicability of the human physiological relevance of preclinical test systems; provide a battery of translational biomarkers that can be used for quantitative read-across from in vitro systems to man and which relate to intracellular pathways (and systems) relevant to drug toxicity. Led by the University of Liverpool, TransQST brings together 14 partners, characterized by their scientific rigour and proven track record. Collectively they will enable achievement of the goals of the call, thanks to their complementarity, proven ability to work together (and with EFPIA partners), and their understanding of how to ensure the relevance of QST to human biology.