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Kurzfassung

• Targeted tumor therapy for highly aggressive pancreatic cancers
• Particularly suited for combinational therapy
• Targeted therapies for human solid tumors bearing wild-type TP53

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Hintergrund

Pancreatic cancer is one of the most aggressive malignancies worldwide, with around 459,000 new cases each year and a 5-year survival rate of only 9%. At the time of diagnosis, surgical removal of the malignant tissue is no longer possible in 80-90% of patients, due to the size of the tumor. The treatment consists of a combination of chemotherapy and targeted therapy but this approach can only extend the patient’s life for a few months and the side effects are considerable. There is a pressing need for new therapeutic options for this highly malignant tumor entity.

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Bilder & Videos

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Lösung

In tumor cells, but not in normal tissue, the protein Agr2 is needed to transport RNA polymerase II into the nucleus. Our innovation describes a liposome-encapsulated hexapeptide, which prevents the binding of RNA polymerase II to Agr2, which in turn causes a general inhibition of transcription specifically in tumor cells and a resulting upregulation of the tumor suppressor gene TP53.

While TP53 is frequently found mutated in tumors, one third of pancreatic carcinomas show the gene in wild-type form. In these tumors, expression of TP53 is inhibited during the transition from acinar ductal metaplasia (ADM) to intraepithelial neoplasia (PanIN) lesions.

In a mouse model, the inventor has been able to show that the formation of PanIN lesions can effectively be inhibited by injecting the liposome-encapsulated hexapeptide. In addition, when combined with another RNA polymerase II inhibitor, - an α-amanitin-conjugated anti-EpCAM antibody - a clear tumor regression could be shown in a xenograft mouse model. Initial cell culture experiments also suggest that the synergistic effect of hexapeptide and α-amanitin could also be used for the treatment of TP53 wild-type colon, lung and breast carcinomas.

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Anwendungsbereiche

• Targeted tumor therapy for highly aggressive pancreatic cancers
• Excellently suited for combinational therapy
• Targeted therapies for human solid tumors bearing wild-type TP53