DIOPTRA aims to introduce a front-line screening tool that will consider risk factors and protein biomarkers for pinpointing individuals at a high risk for colorectal cancer (CRC) incidence. Tissue & blood samples will be examined towards a discriminative set of prognostic proteins that are detectable via standard bloodwork and can indicate a need for further evaluation (i.e. colonoscopy). Other data (e.g. medical, behavioural) will also be considered as potential risk factors. Artificial intelligence (AI) will be leveraged for assessing prognostic power, while personalised behavioural change will be promoted based on modifiable risk factors. Given the low citizen participation on CRC screening across EU, DIOPTRA seeks to broaden the evaluated population, boosting participation rates and bypassing age screening thresholds. This action is part of the Cancer Mission cluster of projects on ‘Prevention, including Screening’.

The SHIELD project seeks to revolutionise early detection of pancreatic cancer, focusing on individuals with high heritable genetic risk. Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of less than 10%, primarily due to late-stage diagnosis. Consequently, 85% of PDAC cases are identified too late for curative treatment. However, early detection can significantly improve outcomes, increasing the survival rate to 42% with surgical intervention. There is a pressing need for better early detection methods, especially for those with familial or genetic predispositions. The only FDA-approved biomarker, CA19-9, is limited to monitoring treatment response due to its lack of sensitivity and specificity, while imaging methods ofter fail to detect early-stage cancers and cause a strain to the healthcare system due to their cost and limited availability. SHIELD aims to validate a new blood-based diagnostic test designed for early PDAC detection in high-risk individuals and pilot an early detection programme in Greece, Slovenia and Lithuania. Developed by partner Reccan, this test uses a 5-plex multiple immunoassay to analyze protein readouts and provides a probability score for pancreatic cancer. Initial studies with over 450 samples showed excellent performance with >91% sensitivity and >96% specificity. The project will validate the test's clinical performance in a prospective multi-center study across seven EU countries, targeting individuals with familial or genetic predispositions. It will also identify new protein biomarkers for other high-risk indications, such as new-onset diabetes (NOD). Collaboration with national screening authorities will help integrate this test into existing programs, and partnerships with patient organizations will enhance recruitment. SHIELD envisions transforming pancreatic cancer diagnostics by increasing the 5-year survival rate to 30% by 2035 in Europe. This action is part of the Cancer Mission cluster of projects on “Prevention & early detection (early detection heritable cancers)

Novel treatment options and associated personalised, patient-tailored therapies need to be explored and developed for highly heterogeneous and chemotherapy resistant cancers, such as malignant melanoma. This can only be achieved by industry-academia collaborations in newly emerging, innovative research disciplines such as translational cancer systems biology and systems medicine. These disciplines and the associated European training needs provide the foundation for the MEL-PLEX ETN. MEL-PLEX aims to understand the network-level and multi-scale regulation of disease-relevant signalling in melanoma through a combination of quantitative biomedical and computational research approaches that go significantly beyond the current state-of-the-art. Coordinated by the RCSI Centre for Systems Medicine, MEL-PLEX will train 15 early stage researchers through a highly interdisciplinary and intersectoral research training programme. MEL-PLEX comprises 11 beneficiaries and 7 partner organisations from 11 countries, including European and international leaders in personalised melanoma therapy, melanoma systems biology and cancer systems medicine. MEL-PLEX aims to (i) achieve an unmatched depth of molecular and mechanistic disease understanding, (ii) will exploit this knowledge to develop and validate predictive models for disease progression, prognosis and responsiveness to current and novel (co-)treatment options, and (iii) will provide superior and clinically relevant tools and biomarker signatures for personalising and optimising melanoma treatment. The MEL-PLEX ETN addresses current needs in academia and the private sector for researchers that have been trained in an environment that spans across biology, medicine and mathematics, that can navigate confidently between clinical, academic and private sector research environments, and that have developed an innovative and creative mindset to progress research findings towards applications.

Breast and colorectal cancer (BC and CRC) are the most frequent cancers accounting for 19% of all deaths from cancer in Europe. In case of triple-negative BC (TNBC) targeted therapies are not available and non-selective chemotherapy is the only treatment option. Targeted therapy has been approved for the treatment of advanced CRC, but response rates are low and treatment is limited to a subgroup of patients. Also, TNBC and CRC patients are prone to develop metastases and have a poor prognosis underpinning the need for new targeted and broadly applicable therapeutic strategies. Tumor cell secretion contributes to hallmarks of cancer e.g. hyperproliferation, evasion of growth suppression, loss of cell polarity, activation of cell motility, invasion and metastasis, shaping of the tumor microenvironment through altered presentation of proteins and the secretome, and resistance to cell death. Dysregulated secretion is thus a driver of cancer progression and therefore holds promise as a general therapeutic target for the treatment of cancers. However, strategies to exploit the secretory pathway for therapeutic and diagnostic purposes are still in their infancy due to the incomplete understanding of how this pathway is regulated by aberrant signaling. The overall research objective of SECRET is to drive the understanding of the mutual regulation of the secretory pathway and signaling in cancer, which will serve as a platform to identify and interrogate novel diagnostic and therapeutic strategies. SECRET comprises 11 beneficiaries and 7 partner organizations from 9 countries. Coordinated by the University of Stuttgart, SECRET will train 15 talented ESRs in the field of translational cancer systems cell biology and systems medicine towards a career in industry or academia through a highly interdisciplinary and intersectoral research training programme and inspire them to exploit the SECRETory pathway as a treasure trove to design novel therapeutic strategies against cancer.

The European community requires early stage researchers (ESRs) who can work across the boundaries of traditional disciplines, integrating experimental and in silico approaches to understand and manage complex multifactorial disorders. This training network utilises intervertebral disc degeneration (LDD) leading to low back pain (LBP) as a relevant application for data integration and computational simulations in translational medicine. LBP is the largest cause of morbidity worldwide, yet there remains controversy as to the specific cause leading to poor treatment options and prognosis. LDD is reported to account for 50% of LBP in young adults, but the interplay of factors from genetics, environmental, cellular responses and social and psychological factors is poorly understood. Unfortunately, the integration of such data into a holistic and rational map of degenerative processes and risk factors has not been achieved, requiring creation of professional crosscompetencies, which current training programmes fail to address. Disc4All aims to tackle this issue through collaborative expertise of clinicians; computational physicists and biologists; geneticists; computer scientists; cell and molecular biologists; microbiologists; bioinformaticians; and industrial partners. It provides interdisciplinary training in data curation and integration; experimental and theoretical/computational modelling; computer algorithm development; tool generation; and model and simulation platforms to transparently integrate primary data for enhanced clinical interpretations through models and simulations. Complementary training is offered in dissemination; project management; research integrity; ethics; regulation; policy; business strategy; and public and patient engagement. The Disc4All ESRs will provide a new generation of internationally mobile professionals with unique skill sets for the development of thriving careers in translational research applied to multifactorial disorders.