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

促性腺激素释放激素受体（Gonadotropin Releasing Hormone Receptor, GnRH-R）的表达主要局限于垂体和生殖器官。值得注意的是，GnRH-R可以在来自GnRH-R阴性组织的肿瘤中检测到。因此，GnRH-R是一个很有前景的靶向治疗环体。GnRH-R在非霍奇金淋巴瘤（NHL）和尿路上皮癌的恶性发展和扩散中的作用尚未确定。因此，应在这些恶性肿瘤中进行GnRH-R的功能鉴定。GnRH-R活性对亚细胞钙稳态、信号转导途径以及细胞迁移和侵袭的影响有待研究。转染过表达可以阐明GnRH-R对恶性转化的影响。此外，GnRH-R和表皮生长因子受体之间的潜在相互作用在尿路上皮癌中的影响将被研究。与EGFR阴性NHL的比较可以发现信号转导中的差异和共同结构。GnRH-R的治疗潜力将通过受体刺激、抑制和细胞毒性gnrh -类似物治疗来评估。为了克服原发性或继发性耐药，GnRH类似物与EGFR抑制剂的平行和串行联合治疗特别有趣。

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.