LHRH (GnRH) receptor targeted tumor chemotherapy

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

The LHRH receptor can be utilized for targeted chemotherapy with cytotoxic LHRH analogs such as AN-152, in which doxorubicin is linked to [D-Lys6]LHRH. Our studies demonstrate receptor-mediated actions of the cytotoxic LHRH analog AN-152 in LHRH receptor positive endometrial and ovarian tumors in vivo. Intravenous administration of AN-152 is far less toxic and inhibits the growth of LHRH receptor-positive tumors better than equimolar doses of cytotoxic agent doxorubicin. In LHRH receptor-negative cancers, AN-152 has no antitumor activity. This provides evidence for the principle of targeted cytotoxic chemotherapy to tumor cells expressing LHRH receptors. In addition, we could show that LHRH binding sites were only slightly reduced after AN-152 treatment. Therefore, repeated therapy is considered to be possible. The majority (80%) of human endometrial and ovarian cancers express LHRH receptors. In addition, apart from reproductive organs which are normally removed during surgical therapy, other organs and hematopoetic stem cells do not express LHRH receptors. Thus cytotoxic LHRH analogs such as AN-152 appear to be suitable drugs for a more efficacious and less toxic targeted chemotherapy for endometrial and ovarian cancers. Our findings are a basis for a further evaluation in clinical trials.

Clinical Trial Phase II: "Antitumoral activity and safety of AEZS-108-040 (AN-152) in women with LHRH receptor positive gynecological tumors"
Study Start Date: December 2007

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