SYSTEMS MEDICINE OF METABOLIC-SIGNALING NETWORKS

A New Concept for Breast Cancer Patient Stratification

Source: National Cancer Institute \ Dana-Farber Harvard Cancer Center at Massachusetts General Hospital
Creator: Sheheryar Kabraji, Sridhar Ramaswamy

Breast cancer is a complex disease with high prevalence in the European Union and world-wide. 75-80% of the patients have estrogen receptor-positive (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 will establish predictive pipelines for

Patient stratification prior and during endocrine therapy

Recurrence risk assessment when ending endocrine therapy

Marker panels to guide established targeted therapies for endocrine therapy-resistant patients

Novel ET resistance mechanism-based therapy design

MESI-STRAT is a 57 months project 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.

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.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 754688.

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