Spatial and multi-omics characterization of single cells to overcome treatment resistance in cancer

Project manager: Xavier Tekpli, Department of Medical Genetics, Division of Laboratory Medicine
Head of the Breast Cancer Heterogeneity and Oncoimmunology project group

Co-project manager: Thomas Fleischer, Department of Cancer Genetics, Institutt for kreftforskning, Division of Cancer Medicine
Head of the Epigenomics of Breast Cancer project group

Resistance to treatment is the principal limitation for curing cancer patients. While macroscopically, patient’s response to treatment may look satisfactory, only a few cells may have acquired resistance and are sufficient to initiate relapse. We therefore aim at analyzing each single cell of breast tumors at different molecular levels (multi-omics) to identify in single cells the mechanisms leading to treatment resistance.
Moreover, we hypothesize that for a cancer cell to become resistant to therapies, it needs to receive signals and support from the surrounding cells of the tumor microenvironment. Cancer, immune, fibroblasts and endothelial cells interact and communicate to build local ecosystems. We will characterize such tumor ecosystems using spatial resolution methods and assess their role in treatment resistance.
To bring our results from single cell and spatial resolution analyses of breast tumors closer to clinical practice and personalized medicine, we culture patient derived organoids to have the possibility to test new treatment strategies for patient relapsing or resistant to therapies directly on their corresponding ex-vivo tumor organoids.