The clinical behaviour and potential management strategies for ovarian cancer subtypes are shaped by anatomic and biologic considerations, with the main determinants of biology being cell context and mutation. We are building on our key ovarian cancer mutation discoveries to investigate the basis of pathogenicity with the goal of using this information to improve treatment. Due to the histogenic specificity of the phenotypes, our lab is undertaking functional studies performed model systems derived from the appropriate cells of origin. Examples of this research include the use a 3D organoid culture system from primary endometrial epithelium to study factors that influence differentiation and the oncogenicity of mutations found in endometriosis and clear cell and endometrioid ovarian cancers. Using xenograft and transgenic murine models, we are studying both the cells of origin of the cancers as well as validating potential drug targets in these systems.
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