Functional Characterization and Preclinical Evaluation Group
The group has two main focuses:
- Functional characterization of factors involved in breast cancer development and progression
- Pre-clinical testing and evaluation of novel drug and drug combinations.
For our studies we are mainly using human cancer cell lines or in vivo models where human breast cancer cells grow in the mammary fat pad of immunedeficient mice (xenograft models). In addition we have access to transgenic models well suited to investigate breast cancer development. Two limitations with the xenograft and transgenic models are the lack of immune system and the fact that we are investigating murine tumor development, respectively. Thus, a prioritized effort in the future is to establish “humanized animal models”. In such models the mouse bone marrow is replaced by human cells, enabling reconstitution of a human immune system, and if bone marrow from the same cancer patient is used this might be an important tool for in vivo testing in personally-adapted cancer medicine.
In the breast cancer cell lines, candidate factors (oncogenes, tumor suppressor genes, metastasis-associated proteins, signal transduction molecules etc) can be knocked down or overexpressed and functional consequences assessed. In vitro mono-cultures or co-cultures with stromal cells are also used for investigation of molecular and functional effects after external stimulation, for instance from microenvironmental factors and therapeutic drugs.
The orthotopic breast cancer models have been demonstrated to resemble their corresponding human tumors in molecular signatures, morphology and metabolism. The models thereby constitute important model systems for pre-clinical evaluation of novel treatment modalities. The models are also used to study tumor heterogeneity and subpopulation dynamics after treatment. The institutional Section for Comparative Medicine is well equipped for in vivo imaging studies (small-animal MRI, fluorescence and bioluminescence imaging system and access to small-animal PET), enabling assessment of tumor physiology, vasculature and metabolism in addition to the ordinary growth measurements. Tumor material from the animals may also be harvested and subjected to pathological and molecular analyses at different levels (collaboration with the Integrated Genomics Group) to search for predictive markers or novel therapeutic targets. For metabolomics studies we are collaborating with the MR Cancer Group headed by Prof Tone Bathen Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU).
- Gunhild Mari Mælandsmo, PhD, group leader. Email: gmn(a)rr-research.no
- Lina Prasmickaite, PhD
- Mads Haugland Haugen, PhD
- Olav Engebråten, MD PhD
- Siri Juell, MSc
- Solveig Pettersen, MSc
- Geir Frode Øy, MSc
- Lisa Gregusson Svartdal, MSc