Research intratumor heterogeneity (ITH)
Genomics-informed clinical decision making and immune therapy have radically changed the therapeutic landscape of cancer. However, the current implementation of these approaches does not incorporate multidimensional intratumor heterogeneity (ITH) responsible for therapy resistant and metastatic clones. This unmet need will be addressed by the multidisciplinary SATURN3 consortium in three common, hard-to-treat tumor entities:
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breast (Luminal-B, TNBC),
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colorectal and
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pancreatic cancer.
SATURN3 will pioneer innovative sample breakdown in order to comprehensively map unique patient cohorts to dissect dynamic ITH over space and time by coupling single-cell, spatial and bulk multi-omics profiling as a central technology in combination with innovative sample processing, liquid- and imaging-based monitoring. We will devise state of the art (including AI-driven) analytical methods to integrate these data, thereby decomposing tumors at unprecedented resolution, uncovering causal relationships, and identifying genetic and non-genetic tumor states that are dynamically altered across tumor evolution and in response to treatment, thereby pinpointing the next generation of biomarkers for translation that captures ITH. Innovative multisite organoid models will be instrumental to dissect ITH-mediated resistance mechanisms and metastasis and identify therapeutic targets. Rigorous validation in large trial cohorts will help select robust biomarkers and the best therapeutic strategies for clinical use. Prospective study protocols will be established to improve treatment and patient survival. SATURN3 is conceptualized by researchers from 13 cancer centers. It integrates a unique team of world-leading omics, data science, translational researchers with biomarker expertise in tissue, fluid and imaging scenarios. Renowned clinicians mandating large study groups will ensure clinical proof-of-concept. SATURN3 is supported by trained patient advocates to promote a patient-centered view. The seamless integrated network structure that connects our working groups will synergize towards the overall goal: rapid translation of profound ITH insights into patientcentered, life-saving therapies.
An overview of the research structure of SATURN3 is shown in the following graph:
