Daria Martin, Schering Stiftung Projektraum

 

Walter Hohlweg Prize 2008

Dr. Jörg Engel

Wuerzburg University Gynecological Hospital

Preclinical Studies of Receptor-Mediated Tumor Therapy with Peptide Hormone Analogues

In September 2008, Dr. Jörg Engel, assistant medical director at the Wuerzburg University Gynecological Hospital, was awarded the 2008 Walter Hohlweg Prize by the German Society of Gynecology and Obstetrics. The €8,000 prize was funded by the Ernst Schering Foundation. Engel was honored for his “Preclinical Studies of Receptor-Mediated Tumor Therapy with Peptide Hormone Analogues.”

In his work, Engel showed that receptor-mediated therapy (“targeted therapy”) with cytotoxic GnRH, bombesin/GRP and somatostatin analogues in preclinical tumor models is highly effective while showing little hematoxicity. In the presented studies, the hybrid molecule in the examined tumor diseases was significantly more potent than the “non-targeted” 2-pyrrolinodoxorubicin. The high effectiveness in highly different tumor entities, such as malignant melanoma and endometrial cancer, indicates that the potential therapeutics might be applied widely. The expression of the specific target receptor on tumor cells, however, is a sine qua non for an effective therapy, because blocking the tumor receptors always led to a significantly reduced effectiveness of the cytotoxic peptide analogues. In all experiments, the hematoxicity following receptor-mediated chemotherapy was lower than following undirected therapy with cytotoxic radical. There is little indication of a fast development of chemotherapeutic resistance following receptor-mediated therapy, because no experiment has shown an increased expression of MDR proteins after treatment. With AN-152, one of the investigated therapeutics is now being tested in clinical trials. In a phase-1 trial with patients with GnRH-receptor positive mammal, ovarian and endometrial cancer, AN-152 was well-tolerated and is now tested for its effectiveness in phase-II trials.

In further studies, it could be shown that the peptide hormone GHRH, originally a hypothalamic peptide, is likely to function as an autocrine growth factor in non-Hodgkin lymphomas and endometrial carcinoma. In-vitro studies and animal models showed that interrupting this autocrine loop through GHRH antagonists inhibits growth in both tumor entities.

Jörg Engel

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