Endokrine Therapie der Zukunft: "magic bullets" und andere Ansätze

This article reviews the recent literature on directed systemic tumor therapy based on antagonists of gonadotropin-releasing hormone (GnRH) and growth hormone-releasing hormone (GHRH) as well as analogs of GnRH as carriers for chemotherapeutic agents. Human breast cancer is known to express receptors for GnRH and GHRH in 50% and 35% of the cases, respectively. The expression and the growth-stimulating effect of GnRH and GHRH ligands have been previously described for breast cancer. Thus, targeted therapy with antagonistic analogs of these peptide hormones is a promising option in this tumor entity. Alternatively, GnRH receptors on breast cancer cells can be used as target structures for cytotoxic hybrid molecules comprising an agonistic analog of GnRH and a cytotoxic radical. This therapeutic approach aims at achieving a higher concentration of the cytotoxic radical in the vicinity of the tumor, thus maximizing antitumor effects and minimizing unwanted side effects. The recent preclinical and clinical data on this subject are reviewed.