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Systems Medicine of Metabolic-Signaling Networks: A New Concept for Breast Cancer Patient Stratification

Systems Medicine of Metabolic-Signaling Networks: A New Concept for Breast Cancer Patient Stratification

Objective

Breast cancer (BC) is a complex disease with high prevalence in the EU. 75% of the tumors are estrogen receptor-positive (ER+), and are treated with endocrine therapies (ET). MESI-STRAT will develop new concepts for knowledge-based stratification of patients into subgroups with different ET resistance mechanisms. We will establish predictive models for (1) patient stratification prior and during ET; (2) recurrence risk assessment when ending ET; (3) marker panel development to guide targeted therapies for ET-resistant patients; (4) novel ET resistance mechanism-based therapy design.

The unique collection of matched BC tissue, serum, and >10 years follow-up from the patient organization PATH is essential for the longitudinal analysis of ET resistance and relapse. Our 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 (MESI) networks driving ET resistance. Metabolite marker panels measured in biological fluids will enable patient stratification, resistance monitoring and clinical decision-making. This is a new concept as BC 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 our clinical and industrial partners in clinical studies. Our 3 SMEs will closely co-develop the research, and directly exploit the MESI-STRAT results.

BC accounts for the highest cancer-related health-care costs in the EU. Our stratification concepts will increase cost effectiveness and the patients’ quality of life by (1) avoiding ineffective therapies, (2) marker detection in body fluids without surgical interventions, and (3) reducing clinical trial cohorts by improved stratification. This will accelerate the translation of MESI-STRAT results into medical use.

Coordinator

UNIVERSITAET INNSBRUCK

Address

Innrain 52
6020 Innsbruck

Austria

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 609 163,13

Participants (14)

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STIFTUNG PATIENTS TUMORBANK OF HOPE- DIE PATIENTENEIGENE TUMORGEWEBEBANK DER HOFFNUNG (PATH)

Germany

EU Contribution

€ 250 550

UNIVERSITATSKLINIKUM HEIDELBERG

Germany

EU Contribution

€ 353 682,50

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

Germany

EU Contribution

€ 870 100

FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON

Spain

EU Contribution

€ 190 956,25

DE DUVE INSTITUTE

Belgium

EU Contribution

€ 289 000

UNIVERSITETET I BERGEN

Norway

EU Contribution

€ 679 520

UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET

Norway

EU Contribution

€ 366 925

UNIVERSITY OF NEWCASTLE UPON TYNE

United Kingdom

EU Contribution

€ 258 687,50

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Germany

EU Contribution

€ 398 706,25

UNIVERSITY OF DURHAM

United Kingdom

NEUROIMMUN GMBH

Germany

EU Contribution

€ 131 750

SYSBIOSIM BV

Netherlands

EU Contribution

€ 102 711,25

HITS GGMBH

Germany

EU Contribution

€ 224 687,50

ACADEMISCH ZIEKENHUIS GRONINGEN

Netherlands

EU Contribution

€ 223 524,37

Project information

Grant agreement ID: 754688

Status

Ongoing project

  • Start date

    1 January 2018

  • End date

    30 September 2022

Funded under:

H2020-EU.3.1.1.

  • Overall budget:

    € 5 949 963,75

  • EU contribution

    € 5 949 963,75

Coordinated by:

UNIVERSITAET INNSBRUCK

Austria