The overall goal of DISCERN is to understand the causes of three poorly understood cancers in Europe; renal, pancreatic and colorectal cancer, and help to explain their geographical distribution, including their high incidence in central and eastern Europe. This will be achieved by combining large-scale European biorepositories comprising population-based cohorts and tumour case-series with state-of-the-art molecular profiling techniques and machine learning approaches. In particular, DISCERN will identify potential new causal risk factors for the three cancers using novel exposomics and proteomics scans, as well detailed geospatial and environmental exposure information from 16 large-scale epidemiological cohorts including almost 900,000 individuals. It will also explore biological mechanisms on how these risk factors are potentially causing these cancer types with a focus on promoting factors in normal tissues using deep sequencing, single cell multi-omics and spatial proteomics. The causal effects of identified cancer risk factors and the cellular signalling responses they trigger will be further evaluated using a panel of stem cells and colon, renal and pancreatic 3D organoids. The results from DISCERN will be disseminated to citizens, patients and policy makers through collaborating patient and participant organizations. DISCERN will provide the critical evidence base required to develop new prevention strategies to tackle the growing burden of renal, pancreatic and colorectal cancer in Europe. This action is part of the Cancer Mission cluster of projects on "Understanding".

Pancreatic cancer (PDAC) is usually detected at late stages and most patients die within one year after diagnosis. In PANCAID we will therefore develop a blood test for early detection of PDAC. Despite tremendous technological advances in Liquid Biopsy Diagnostics (LBx), this goal is very ambitious because small tumors release only minute amounts of cells or cellular products (e.g., DNA, RNA, protein, metabolites) into the circulation. Thus, tests with a high sensitivity are required but increases in sensitivity are usually achieved on the expenses of reduced specificity which can lead to significant overdiagnosis leading to unnecessary stress for the individuals with a false-positive blood test and high costs for the health system. In PANCAID, we will therefore establish a blood test with high accuracy by analyzing large cohorts of patients with PDAC and its precursor lesions, individuals at risk to develop PDAC and appropriate age-matched control groups (healthy and non-cancer diseases frequent in the targeted population). Ambitious objectives of PANCAID include (1) establishment of a unique resource of blood samples of early PDAC and risk groups (WP1); (2) Establishment of a breakthrough blood test for early diagnosis of PDAC (WP2); (3) Identification of the best composite biomarker panel by integrating multimodal features in an AI-assisted computational analysis; (4) Analysis of the socio-economic impact of early PDAC diagnosis (WP4); and (5) Definition of the ethics parameters relevant to early PDAC detection (WP5). A robust multi-biomarker panel will be determined during the training period (year 1-3) and subsequently validated on bio-banked blood samples (year 4-5). Depending on the outcome of this comprehensive analysis, PANCAID will provide the design of a future prospective study for validation of the developed composite blood test in an international multi-center setting required to introduce LBx into screening programs for high-risk individuals. This action is part of the Cancer Mission cluster of projects on ‘Prevention, including Screening’.