Hormone therapy using GnRH-II antagonists

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Group Leaders: Prof. Dr. rer. nat. Carsten Gründker, Prof. Dr. med. Günter Emons

In human endometrial, ovarian and breast cancers, GnRH-I, GnRH-II and their receptors are parts of a negative autocrine regulatory system of cell proliferation. Induction of apoptosis is not involved in the antiproliferative effects of GnRH-I or GnRH-II agonists.
We have developed and ascertained the effects of antagonists of GnRH-II. Treatment with GnRH-II antagonists resulted in apoptotic cell death via dose-dependent activation of caspase-3. The anti-tumor effects of the GnRH-II antagonists could be confirmed in nude mice. GnRH-II antagonists inhibited the growth of xenotransplants of human endometrial, ovarian and breast cancers in nude mice significantly, without any apparent side effects.
Thus GnRH-II antagonists appear to be suitable drugs for an efficacious and less toxic endocrine therapy for endometrial, ovarian and breast cancers.

Funding:

• Deutsche Krebshilfe - Dr. Mildred Scheel Stiftung, approved on 08/18/2004 for 2 years

• Deutsche Krebshilfe - Dr. Mildred Scheel Stiftung, approved on 01/22/2007 for 2 years

Publications:

• Fister S, Günthert AR, Emons G, Gründker C (2007) Gonadotropin-releasing hormone type II antagonists induce apoptotic cell death in human endometrial and ovarian cancer cells in vitro and in vivo. Cancer Research 67:1750-1756

• Fister S, Günthert AR, Aicher B, Paulini KW, Emons G, Gründker C (2009) GnRH-II antagonists induce apoptosis in endometrial, ovarian and breast cancers via activation of stress-induced MAPKs p38 and JNK and pro-apoptotic protein Bax. Cancer Research 69:6473-6481

• Gründker C, Föst C, Fister S, Nolte N, Günthert AR, Emons G (2010) GnRH-II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo. Breast Cancer Research 12(4):R49

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Hormone therapy using cotreatment of GnRH-II antagonists with anti-estrogens/SERMs

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Antitumor efficacy of Tamoxifen in breast cancer cells in vitro and in vivo is potentiated by cotreatment with GnRH-II antagonists.

Funding:

• Deutsche Krebshilfe - Dr. Mildred Scheel Stiftung, approved on 07/24/2009 for 2 years

Publications: