Project: Resistance under treatment in breast cancer

Acronym RESCUER (Reference Number: ID39)
Project Topic Breast cancer (BC) is the first cause of cancer-related death in women worldwide. Breast cancer is classified into well-recognized molecular subtypes. Despite solid pre-clinical evidence, only some patients benefit from administering drug combinations, an indication that patient and tumor heterogeneity is still present in the current stratification. Out of the numerous possible combinations of approved drugs, only a few have been actually tried, and the choice of tested combinations has been to some degree arbitrary. This proposal seeks to develop new approaches and identify mechanisms of treatment resistance at systems level, exploring how the effectiveness of specific targeted therapies applied in different clinical trials is affected by patient- and tumor-specific conditions. For this purpose, the project will gather and integrate longitudinal multidimensional data from ongoing clinical trials and newly generated -omics using systems approaches, which combine sub-cellular/cellular and/or organ level in silico models and network analysis to build computational frameworks able to discover molecular signatures of resistance and predict patient response to combinatorial therapies. We aim to identify the physiological characteristics of non-responders vs. responders from existing and newly generated multi-omic data and biological samples from in vivo and ex vivo clinical studies of specific subtypes of BC patients treated with combination therapy. This new knowledge will be used to investigate the curative potential of new personalized drugs combinations. The overreaching goal is to develop computer “xenograft model” as a costefficient and better alternative in terms of ethics, availability to everyone, and animal use. The framework will include optimization algorithms to identify combinations of approved drugs with a high probability to work on individual or thin strata of patients.
Network ERAcoSysMed
Call 3rd Joint Transnational Call for European Research Projects on Systems Medicine

Project partner

Number Name Role Country
1 University of Oslo Coordinator Norway
2 Centre National de Recherche en Génomique Humaine Partner France
3 University Hospital Erlangen Partner Germany
4 University of Leuven Partner Belgium
5 Cancer Research Insitute BMC SAS Partner Slovakia
6 Oslo University Hospital Partner Norway
7 OZ MAMMA FEMININA Observer Slovakia