Ein systematischer Ansatz zur Identifizierung, Isolation und Validierung von Ovarialkarzinomstammzellen

• Antragstellerin: Dr. Anne Kathrin Volkmer
• Fachliche Zuordnung: Gynäkologie und Geburtshilfe
• Förderung: Förderung von 2012 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 227988416

Ovarian cancer (OC) accounts for about 3% of all cancers among women and ranks second among gynecologic malignancies. Epithelial ovarian carcinoma (EOC) accounts for nearly 90% of all ovarian neoplasms, circa 60-80% are serous papillary carcinomas, appearing histologically similar to normal fallopian tube tissue. OC causes more deaths than any other cancer of the female reproductive system, it ranks fifth in cancer deaths among women. Due to unspecific symptoms and the lack of screening methods primary diagnosis is mostly in advanced stages FIGO III and IV with a poor 5-year survival rate of 23% and 14% respectively. After good initial response to standard treatment of tumordebulking and platinum based chemotherapy, the majority of these patients suffer from local or disseminated relapse. One potential explanation for this frequent progression and recurrence is the failure of current therapies to effectively target and eliminate ovarian cancer stem cells (CSCs) that are ultimately responsible for the initiation, maintenance, and expansion and propagation of the tumor. Therefore is a need to characterize and understand the behavior of every single cell within the tumor. This project proposes a novel approach to understand the heterogeneity within serous OC (SOC) by organizing the different subpopulations in a hierarchically order. We will utilize a biologically supervised computational approach to mine the extensive repertoire of publicly available expression array data to define signatures of cellular differentiation in SOC. The cellular subpopulations defined by the identified markers will be further functionally validated in vitro and in vivo for their hierarchical order to identify the tumorigenic subset, the CSC population on top of this hierarchy. Subsequently, the association of the markers defining the CSCs with patient outcome will be analyzed. This will lead not only to better diagnostics but moreover to novel therapies against CSCs, which will improve the outcome of SOC patients.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeber: Professor Dr. Irving L. Weissman