Functional characterization of Gonadotropin Releasing Hormone Receptor (GnRH-R) in Non Hodgkin´s Lymphoma (NHL) and Urothelial Carcinoma- a novel therapeutic target

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The expression of the Gonadotropin Releasing Hormone Receptor (GnRH-R) is mostly limited to the pituitary gland and the reproductive organs. Remarkably, GnRH-R can be detected in tumors which originate from GnRH-R negative tissues. Thus, GnRH-R is a promising loop whole for targeted therapy. The role of GnRH-R in malignant development and spreading of non hodgkin´s lymphoma (NHL) and urothelial carcinoma has not been determined yet. Therefore, functional characterization of GnRH-R shall be carried out in these malignancies. The influence of GnRH-R activity on subcellular calcium homeostasis, signal transduction pathways as well as on cell migration and invasion is to be examined. Overexpression by transfection shall clarify the influence of GnRH-R on malignant transformation. Furthermore, the impact of a potential interaction between GnRH-R and Epidermal Growth Factor Receptor is to be investigated in urothelial carcinoma. A comparison with EGFR negative NHL allows to find differences and common structures in signal transduction. The therapeutic potential of GnRH-R will be evaluated by receptor stimulation, inhibition and treatment with cytotoxic GnRH-analogs. Parallel and serial combination therapies of GnRH analogs with EGFR inhibitors are of particular interest in order to overcome primary or secondary resistance.