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.