Preclinical evaluation of targeted therapies in endometrial cancer: use of primary in vitro and in vivo models.

Endometrial cancer is the most frequent malignancy of the female genital tract and the fourth most frequent cancer in women in the developed world. Treatment modalities for endometrial cancer include surgery, chemotherapy and radiotherapy, but these are limited for primary advanced and recurrent disease leading to a poor overall survival of these patients. Development of new treatment strategies for endometrial cancer is therefore warranted. In this proposal, focus is centered on the identification of specific genetic changes in endometrial cancer, and their role in response to different types of systemic therapies. To this end, primary cell cultures and patient-derived xenografts (PDXGs) from endometrial carcinomas will be established and their molecular and genetic profile will be identified and compared to that of the original primary tumor. Subsequently, the identified molecular/genetic profiles will be linked to their in vitro and in vivo response to different targeted therapies, including targeted therapies against the PI3K/PTEN/AKT and KRAS/EGFR pathway. In summary, this proposal aims to enlarge insight in the molecular and genetic abnormalities in endometrial cancer and their effect on therapy response.