Spatial and Temporal Resolution of Intratumoral Heterogeneity in 3 hard-to-treat Cancers

Objectives

The overall goal of the SATURN³ consortium is to combine unique expertise and most current technologies from basic, translational and clinical research to monitor and treat dynamic intratumor heterogeneity (ITH) in patients.

• Investigate the development of tumor heterogeneity in patients through longitudinal tumor profiling
• Implement standardized single-cell/spatial omics and imaging workflows combined with AI-driven analytics to dissect and characterize intratumor heterogeneity (ITH) in human tumors
• Explore the underlying mechanism generating tumor heterogeneity
• Identify converging principles of intratumor heterogeneity (ITH) within and across entities
• Employ causal and mechanistic modelling to derive candidate hypothesis of ITH associated resistance mechanisms mediated by cellular plasticity, stromal and immune microenvironment as well as many other biological principles.
• This is achieved partly by setting-up mechanistic experiments using patient derived organoids and xenografts and functional CRISPR mediated gene editing screens as well as single cell tracing technologies
• Validation and translation towards personalized treatment concepts
• Direct involvement of the patient perspective in the research work

IMpact

• Development of better therapeutic interventions for three frequent and hard-to-treat cancer types (breast cancer, colorectal cancer, pancreatic cancer)
• Strategies to overcome treatment resistance and metastasis, resulting in a gain in quality-adjusted life years for patients.
• Improved understanding of ITH through longitudinal and spatially annotated (primary tumor, metastases) sampling of cancer tissue and blood from individual cases with the most advanced methodological approaches
• Generate substantial knowledge on how to target ITH and use this knowledge to design innovative clinical trials.