The European Union awards €6 million to a large international research-consortium, called MESI-STRAT, led by Professor Kathrin Thedieck of the University Medical Center Groningen. MESI-STRAT will take almost 5 years and explores the interplay of breast cancer metabolism and oncogenic signaling by systems medicine. MESI-STRAT’s main goal is to develop new models for knowledge-based stratification of patients into subgroups to guide targeted interventions.
Breast cancer is a complex disease with high prevalence in the European Union and world-wide. 75-80% of the patients have estrogen receptor (ER)-positive tumors and are treated with endocrine therapies. Endocrine therapies, which block ER-driven tumor growth, show high efficacy. Yet, a significant proportion of the patients will eventually relapse with metastatic breast cancer, and the recurrence rates remain almost constant for up to 20 years.
Breast cancer metabolism – a new concept for patient stratification
MESI-STRAT develops metabolite marker panels measurable in biological fluids to enable patient stratification, resistance monitoring and clinical decision-making throughout endocrine therapy. This is a new concept as breast cancer metabolism is poorly explored for diagnostics and therapy. Upon successful validation in preclinical models, the predictive marker panels and related treatments will be jointly investigated by MESI-STRAT’s clinical and industrial partners. A unique collection of matched breast cancer tissue, serum, and >10 years follow-up from the patient organization and MESI-STRAT co-coordinator “Patients’ Tumor Bank of Hope” (PATH,
) is essential for the longitudinal analysis of endocrine therapy resistance and relapse.
Research aims and approach
The MESI-STRAT consortium explores the interplay of breast cancer metabolism and oncogenic signaling (MEtabolic SIgnaling) by systems medicine approaches. MESI-STRAT develops new models for knowledge-based stratification of patients into subgroups with different endocrine therapy resistance mechanisms. MESI-STRAT aims to establish predictive pipelines for (i) patient stratification prior and during endocrine therapy; (ii) recurrence risk assessment when ending endocrine therapy; (iii) marker panels to guide established targeted therapies for endocrine therapy-resistant patients; and (iv) novel resistance mechanism-based therapy design.
A pan-European team of oncologists, modelers, bioinformaticians and experimentalists will develop new computational models in combination with network analyses and pharmacogenomics, to integrate multi-omics data and explore metabolic and signaling networks driving endocrine therapy resistance.
MESI-STRAT is a 57 months project (funding volume 5.95 million Euros) coordinated by Prof. Kathrin Thedieck at the University Medical Center Groningen, The Netherlands (UMCG). Dr. Tobias Anzeneder from the German patient organization PATH Biobank is the MESI-STRAT co-coordinator.
14 partners from six European countries contribute to MESI-STRAT: jointly with modelers and experimentalists at the University of Newcastle upon Tyne, UK (Dr. Daryl Shanley) and the Charité in Berlin, Germany (Prof. Christine Sers), work at the UMCG (Prof. Kathrin Thedieck) focuses on oncogenic signaling through the mTOR and MAPK networks. Experimentalists and modelers at the German Cancer Research Center (DKFZ, Dr. Christiane Opitz), the University of Bergen, Norway (Prof. Mathias Ziegler), the Arctic University of Troms ø , Norway (Prof. Ines Heiland) and Neuroimmun GmbH, Karlsruhe, Germany (Dr. Karl-Heinz Kellner) focus on metabolic networks centered on tryptophan and NAD metabolism. Model and data management and analyses are conducted by HITS gGMBH, Heidelberg (PD Dr. Wolfgang Müller) and the University of Durham (Dr. Sushma Grellscheid). SysBioSim B.V. (Basak Tektemur-Altay) in Leiden, The Netherlands customizes our models for the pharma sector. Our computational models are developed, individualized, and validated based on patient derived in vitro and in vivo models from Dr. Violeta Serra (Vall d’Hebron Institute of Oncology, Barcelona, Spain) and Prof. Benoit van den Eynde (De Duve Institute, Brussels, Belgium), and patient samples from clinical trials within and associated with MESI-STRAT. The MESI-STRAT clinical trials are coordinated by the clinician scientist Dr. Christiane Opitz (DKFZ), and conducted by PATH Biobank (Dr. Tobias Anzeneder) and the University Hospital Heidelberg (Prof. Sarah Schott, Prof. Andreas Schneeweiss).
Further reading and contact
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