Rezeptoren für GnRH und GHRH als Prognosefaktoren und therapeutische Zielstrukturen in tripelnegativen Mammakarzinomen
Final Report Abstract
A novel targeted cytotoxic hybrid of GnRH was evaluated with respect to efficacy and mechanism of action, in vitro. Thus, we could clearly show, that the cytotoxic effect of AEZS-125 is linked to GnRH-receptors on TNBC cells. Additionally, treatment combinations for TNBC based on GnRH-and GHRH-analogs and chemotherapeutic agents and novel signal transduction inhibitors were identified. In particular, GnRH-agonist showed synergistic effects with platinum derivatives in TNBC, in vitro. All these above results are currently evaluated in vivo, in collaboration with Prof. Schally, Miami, USA. Recently, the POEM trial was designed to investigate ovarian protection by GnRH-anaolgs in premenopausal hormone receptor negative breast cancer patients bound to receive chemotherapy 5. Interestingly, the investigators found an improved progression-free and overall survival in patients treated with a combination of chemotherapy and GnRH-analogs vs patients treated with chemotherapy alone. Thus, our in vitro studies showing synergistic effects of GnRH-analogs with chemotherapy might actually be of clinical relevance.
Publications
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Triple negative breast cancers express receptors for LHRH and are potential therapeutic targets for cytotoxic LHRH-analogs, AEZS 108 and AEZS 125. BMC cancer 2014;14:847
Seitz S, Buchholz S, Schally AV, Weber, F., Klinkhammer-Schalke, M., Inwald, E. C., Perez, R., Rick, F. G., Szalontay, L., Hohla, F., Segerer, S., Kwok, C. W., Ortmann, O., Engel, J. B.
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Receptors for luteinizing hormone-releasing hormone (GnRH) as therapeutic targets in triple negative breast cancers (TNBC). Targeted oncology 2015 Sep;10(3):365-73
Kwok CW, Treeck O, Buchholz S, Seitz S, Ortmann O, Engel JB
