We study development and progression of breast cancer focusing on the earliest stages and transition from ductal carcinoma in situ (DCIS) to invasive cancer. Through an increased understanding of the cell types from which tumors develop, the signaling pathways perturbed, and the critical events for transition from pre-invasive to invasive stages of the disease, better stratification of patients for treatment can be advised. Also, novel targets for treatment may be tested in mouse models mimicking human disease, a prerequisite for clinical trials. Breast cancer is a complex and heterogeneous disease. Despite improved mortality rates due to better diagnostics and treatment, it is the most common cancer in women with an expected 3000 new cases in Norway annually. An increased incidence of DCIS has been observed coinciding with the introduction of public mammography screening. DCIS represents a spectrum of abnormal cells confined within the lumen of the mammary ducts, many of which will never lead to invasive cancer. Little is known of the natural history of DCIS, there are no specific and robust risk stratification markers, hence, a substantial number of patients are likely over-treated. We are conducting a spectrum of molecular analyses of breast tissue samples ranging from normal tissue to invasive cancer; fresh frozen as well as archived samples from patients. Data from all analyses are thoroughly examined along with clinical data, and similar data from progression models in mice to identify important pathways in the progression of breast cancer and putative markers for risk stratification. Intra-tumor heterogeneity puts an additional layer of complexity to breast cancer diseases and may have important implications for how a tumor reacts to therapy. We use different mouse models that allow us to study separate tumor populations; how they are able to initiate tumors and if they response differentially to treatment. By lineage tracing experiments we are able used to study development of tumors particularly along the Wnt-Hedgehog signaling axis.
- Identify and characterize tumorigenic subpopulations of cells from xenograft models representing various breast cancer subtypes;
- Identify and test novel targetable markers of tumorigenic cell populations in mice models;
- Investigate how Hedgehog signaling influences breast cancer;
- Study the role of GLI1 in tumor formation and LGR5 as a breast stem cell marker;
- Characterize progression pathways of DCIS within different tumor subtypes
- Identify and test potential molecular progression markers in large patient cohorts.