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

About SATURN3

Cancer entities with marked cellular heterogeneity include breast cancer (triple-negative and luminal-B mammary carcinoma), microsatellite-stable colorectal carcinoma and pancreatic ductal adenocarcinoma. Their tremendous cellular and associated molecular heterogeneity allows these tumors to develop metastases and escape current therapies.

In order to develop better treatment options, a better understanding of the underlying mechanisms is needed. These are now being closely examined in the multi-disciplinary SATURN³ project using beyond-state-of-the-art technologies studying patient’s tumor cells at single cell resolution and during the course of the disease.

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