Molecular alterations in metastatic gynecological cancer

Endometrial cancer is the most common and ovarian cancer the most lethal gynecologic malignancies. Improved treatment for metastatic disease and reliable predictors for response to therapeutics are needed. This project is an integrated part of a regional, national and international prospective multicenter study of tissue from primary and metastatic lesions to facilitate implementation of individualized molecularly based targeted therapy. We have recently identified new potential targets for treatment of a ggressive gynecologic cancer such as FGFR2 and the PI3Kinas signaling pathway (Dutt, PNAS 2008 and Salvesen, PNAS 2009). In this project we plan to take our previous studies of global molecular classification of primary tumours to the next level. The hypo thesis is that the corresponding molecular profile of both the primary tumor and the metastatic lesion is relevant for targeted therapy. The aim of the project is to conduct a comprehensive molecular classification of the primary lesion and for a subset o f patients, the corresponding metastatic lesions from the same patient in endometrial- and ovarian carcinomas. These findings will be related to phenotype, chemotherapy response and used to identify alterations in specific signalling pathways potentially targetable by new drugs. The ultimate goal is to apply this knowledge to improve the design of molecularly targeted therapy by contributing novel genetic signatures to phase II trials and hence translate the findings into clinical practice.