Research Mission
Summary
Transforming cancer therapy from a reactive to a proactive strategy
The Collaborative Research Center (CRC) DYNAMO aims to transform melanoma therapy from a reactive to a proactive approach. Its key focus is the early “DYNAMO Window” – the first three weeks of systemic treatment when therapy resistance begins to emerge. By combining patient-derived samples, advanced preclinical models, and AI-driven data analysis, the consortium maps early tumor–microenvironment interactions and identifies dynamic cell states that drive resistance. The goal is to uncover early biomarkers and therapeutic vulnerabilities that allow resistance to be predicted and prevented before it becomes clinically relevant, addressing a major unmet need in cancer treatment.
Conceptual overview
Early tumor cell states and the DYNAMO Window
We will address the question of why distinct melanoma cell states represent early barriers to therapy response. The DYNAMO Window is defined as the read-out window between therapy baseline and week 3 (+/- 7 days) for clinical samples and day 3-7 for pre-clinical samples. This enables us to study pre-determined persister states and immediate cell state dynamics as ‘kick starter’ of resistance, i.e. the balance of cell selection vs. adaption (stochasticity & evolvability). MAPKi=MAP kinase inhibitor, ICI=immune checkpoint inhibitor.
Tumor–microenvironment interactions in the early phase of therapy
We will study (1) how the complex tumor microenvironment contributes as a local predilection site to resistance development and (2) what are the early biological dynamics in the composition and function of prioritized cell types.Multiple stromal (cancer-associated fibroblasts, CAFs; endothelial cells, ECs) and immune cells (T lymphocytes; natural killer (NK) cells; tumor-associated macrophages, TAM; tumor-associated neutrophils, TANs) have been shown to confer resistance in melanoma. Created with BioRender.com
Generating actionable, patient-specific predictions and resistance-targeting interventions
By combining high-resolution multi-omics profiling, advanced computational modeling, and clinically aligned biomarker stratification, DYNAMO will generate actionable, patient-specific predictions and resistance-targeting interventions. Structurally, the CRC is engineered for maximal synergy, leveraging shared data resources, efficient sample use, and a unified translational framework integrated into the Smart Hospital Information Platform (SHIP) of the University Hospital Essen. A key component of this framework is the CRC-integrated biosampling program PROSEQ, a prospective clinical platform that collects paired tumor, blood, and urine samples at baseline and early during therapy from melanoma patients treated at the Department of Dermatology in Essen.
Developing and validating strategies to overcome immediate resistance
Using melanoma as a model tumor, the CRC will develop and validate strategies to overcome immediate resistance to targeted and immune therapies, ultimately maximizing tumor elimination. Over the next 12 years, DYNAMO aims to establish the scientific foundation for an internationally leading, systematic, and globally scalable approach to proactive resistance prevention—setting a new standard for the future of oncology.
