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Article

New Therapy Options for Neuroendocrine Carcinoma of the Pancreas—The Emergent Substance GP-2250 and Gemcitabine Prove to Be Highly Effective without the Development of Secondary Resistances In Vitro and In Vivo

1
Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
2
Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, 44780 Bochum, Germany
3
Geistlich Pharma AG, 6110 Wolhusen, Switzerland
4
Department of General, Visceral and Vascular Surgery, Evangelische Kliniken Gelsenkirchen, Akademisches Lehrkrankenhaus der Universität Duisburg-Essen, 45879 Gelsenkirchen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Zhixiang Wang
Cancers 2022, 14(11), 2685; https://doi.org/10.3390/cancers14112685
Received: 26 April 2022 / Revised: 20 May 2022 / Accepted: 25 May 2022 / Published: 29 May 2022
(This article belongs to the Collection Drug Resistance and Novel Therapies in Cancers)
Neuroendocrine carcinoma of the pancreas is a highly aggressive form of neuroendocrine tumor associated with poor survival and increasing occurrence. GP-2250 is an emergent substance showing antineoplastic properties, especially in combination with Gemcitabine. This study was the first to evaluate the antineoplastic effects of GP-2250 on pancreatic neuroendocrine carcinoma. The combination of GP-2250 and Gemcitabine showed highly synergistic effects in a cell culture model, as well as in mice, without the development of secondary resistances. These findings form the basis for further clinical evaluation of a highly promising combination therapy.
Neuroendocrine carcinoma of the pancreas (pNEC) is an aggressive form of neuroendocrine tumor characterized by a rising incidence without an increase in survival rates. GP-2250 is an oxathiazinane derivate possessing antineoplastic effects, especially in combination with Gemcitabine on the pancreatic adenocarcinoma. The cytotoxic effects of the monotherapy of GP-2250 (GP-2250mono) and Gemcitabine (Gemmono), as well as the combination therapy of both, were studied in vitro using an MTT-assay on the QGP-1 and BON-1 cell lines, along with in vivo studies on a murine xenograft model of QGP-1 and a patient-derived xenograft model (PDX) of Bo99. In vitro, Gemmono and GP-2250mono showed a dose-dependent cytotoxicity. The combination of GP-2250 and Gemcitabine exhibited highly synergistic effects. In vivo, the combination therapy obtained a partial response in QGP-1, while GP-2250mono and Gemmono showed progressive disease or stable disease, respectively. In Bo99 PDX, the combination therapy led to a partial response, while the monotherapy resulted in progressive disease. No development of secondary resistances was observed, as opposed to monotherapy. This study was the first to evaluate the effects of the emerging substance GP-2250 on pNEC. The substance showed synergism in combination with Gemcitabine. The combination therapy proved to be effective in vitro and in vivo, without the development of secondary resistances. View Full-Text
Keywords: neuroendocrine carcinoma; pancreas; chemotherapy; xenograft; secondary resistance neuroendocrine carcinoma; pancreas; chemotherapy; xenograft; secondary resistance
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MDPI and ACS Style

Buchholz, M.; Strotmann, J.; Majchrzak-Stiller, B.; Hahn, S.; Peters, I.; Horn, J.; Müller, T.; Höhn, P.; Uhl, W.; Braumann, C. New Therapy Options for Neuroendocrine Carcinoma of the Pancreas—The Emergent Substance GP-2250 and Gemcitabine Prove to Be Highly Effective without the Development of Secondary Resistances In Vitro and In Vivo. Cancers 2022, 14, 2685. https://doi.org/10.3390/cancers14112685

AMA Style

Buchholz M, Strotmann J, Majchrzak-Stiller B, Hahn S, Peters I, Horn J, Müller T, Höhn P, Uhl W, Braumann C. New Therapy Options for Neuroendocrine Carcinoma of the Pancreas—The Emergent Substance GP-2250 and Gemcitabine Prove to Be Highly Effective without the Development of Secondary Resistances In Vitro and In Vivo. Cancers. 2022; 14(11):2685. https://doi.org/10.3390/cancers14112685

Chicago/Turabian Style

Buchholz, Marie, Johanna Strotmann, Britta Majchrzak-Stiller, Stephan Hahn, Ilka Peters, Julian Horn, Thomas Müller, Philipp Höhn, Waldemar Uhl, and Chris Braumann. 2022. "New Therapy Options for Neuroendocrine Carcinoma of the Pancreas—The Emergent Substance GP-2250 and Gemcitabine Prove to Be Highly Effective without the Development of Secondary Resistances In Vitro and In Vivo" Cancers 14, no. 11: 2685. https://doi.org/10.3390/cancers14112685

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