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.

It is the ambition of PRESIST-SEQ to provide a new gold standard in single-cell experimental workflows the cancer research community by developing best practices, standard operating procedures (SOPs), and high-quality FAIR data, with the ultimate aim to empower them to unravel therapeutic resistance. Such, that the community can identify urgently needed markers to predict, prevent, and target tumour resistance. Cancer takes 9.6 million lives each year, 90% of which result from untreatable metastatic relapse occurring after initially (seemingly) effective treatment. Therapeutic resistance is hence a primary cause of cancer death that clinically cannot be predicted, prevented, or treated. Addressing the urgent need for smarter therapeutic strategies is however held back by the lack of standardised experimental approaches that enable studying the biology of residual disease and drug tolerant persister cells in full detail. This need encompasses best practices for single-cell sequencing, advanced modelling techniques using patient-derived organoids and xenografts, and data FAIRification for integrated experiments. To address this need, PERSIST-SEQ brings together globally leading groups in single-cell sequencing technologies, cancer modelling and therapeutic resistance. Furthermore, the consortium has a broad range of clinical samples, cell lines, 3D models (PDX and PDOs) and mice models (GEMMs) at its disposal that can be leveraged to answer a broad range of emerging questions. This positions the consortium excellently to (1) design and standardise single-cell experimental approach to study the biology of therapeutic resistance and (2) initiate the largest single-cell profiling initiative on therapeutic resistance. Importantly, PERSIST-SEQ is organised such that it can quickly adapt to emerging insights and techniques during the project, and that ensures the capture of learnings in manners that stimulate replication of workflows elsewhere.

Cancer remains the leading cause of disease-related death in children. For the ~25% of children who experience relapses of their malignant solid tumors, usually after very intensive first-line therapy, curative treatment options are scarce. Preclinical drug testing to identify promising treatment options that match the molecular make-up of the tumor is hampered by the facts that i) molecular genetic data on pediatric solid tumors from relapsed patients and thus our understanding of tumor evolution and therapy resistance are very limited to date and ii) for many of the high-risk entities no appropriate and molecularly well characterized patient-derived models and/or genetic mouse models are currently available. Thus, quality-assured upfront preclinical testing of novel molecularly targeted compounds in a (saturated) repertoire of well-characterized models will establish the basis to increase therapeutic successes of these drugs in children with solid malignancies. Since these tumors are overall genetically much less complex than their adult counterparts, it is anticipated that it will be easier to identify powerful predictive biomarkers to allow for accurate matching of targets and drugs. To address this high, as yet unmet clinical need, we have formed the ITCC-P4 consortium consisting of academic and commercial partners from 8 European countries and covering the full spectrum of qualifications needed for quality-assured preclinical drug development including expertise in patient derived models, histopathology, in vivo pharmacology, bioinformatics and data management, centralized testing capabilities, medical expertise regarding the entities in question, regulatory knowledge, and project management of large consortia. With this consortium in a public-private partnership with the participating pharma companies we strongly believe to be ideally positioned to greatly expedite the development of more precise and efficacious drugs for children with malignant solid tumors