Midtveisevaluering - Tina Fonnes
Background: Endometrial carcinoma (EC) is the 4th most common cancer in women in Europe, and relevant animal models are powerful tools in the process of moving towards individualized therapy for this patient group.
Aim: Develop reliable and relevant mouse models to study endometrial cancer, and use these models to test clinically based hypotheses - including molecular function of biomarkers and response to selected therapy.
Methods: Orthotopic mouse models of human endometrial carcinoma have been established, using both cell lines and patient derived xenografts (PDX). The ability of small animal imaging modalities such as bioluminescent imaging (BLI), PET-CT, and MRI to monitor tumor growth in these mouse models have been explored. In an ongoing study, BLI is used to explore the effect of a potential predictive biomarker on therapeutic response in an orthotopic mouse model of EC. An imaging protocol using a fluorescent antibody to detect endometrial carcinoma xenografts is also currently being established. Additionally we are validating the enzyme ASRGL1 as a prognostic biomarker for endometrial carcinoma in independent patient cohorts.
Preliminary results: BLI, PET-CT and MRI are feasible modalities for detection of tumor in a cell line based orthotopic EC mouse model, and PET-CT allows visualization of tumor in PDX-models of EC. Optical imaging using a fluorescent antibody is also able to detect tumor and metastases in a cell line based orthotopic mouse model of EC. In our patient cohorts loss of the enzyme ASRGL1 is found to be significantly associated with poor survival, as well as several clinicopathological features of aggressive disease.
Future plans: The protocol using fluorescent antibodies will be tested in PDX-models of EC, and can potentially be used for monitoring of therapeutic studies in such models. Patient series are currently being expanded, and a possible correlation between ASRGL1 expression and PET-CT findings will be evaluated. The function of ASRGL1 will be further explored through in vitro and in vivo studies.