Rezeptorvermittelte Chemotherapie gynäkologischer Tumoren und des Mammakarzinoms

Abstract

The current article reviews a novel approach in tumor therapy based on peptide hormon analogs of GnRH, Bombesin/GRP and Somatostatin as carrier substances for cytotoxic agents, thus aiming to achieve a higher concentration of the active compound in the vicinity of the tumor. This therapeutic concept should lead to an increased antitumoral efficacy and minimized side effects. Targeted therapy with cytotoxic analogs of GnRH, Bombesin/GRP and Somatostatin has been highly effective in preclinical tumor models of breast-, endometrial, and ovarian cancer, although associated with only a low haematological toxicity. In the current studies cytotoxic hybrid molecules were significantly more potent than the chemotherapeutic agent alone. However, the expression of the respective target receptor on the tumor cells is a necessary requirement for an effective therapy, as blockade of tumoral receptors significantly decreased the efficacy of the cytotoxic hybrid molecules in vivo. The haematological toxicity of targeted chemotherapy was significantly less pronounced than the corresponding nondirected therapy with a cytotoxic radical alone in all animal experiments. The rapid development of a resistance to targeted chemotherapy is unlikely, as the expression of MDR proteins after targeted therapy was not increased as compared to a corresponding non-targeted approach in all experiments. AN-152, one of the compounds investigated in this article has already entered clinical testing. Thus, AN-152 showed a good tolerability in a clinical phase I study for patients with GnRH-positive breast-, ovarian-, and endometrial cancer and is now tested for efficacy in a clinical phase II study.