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Volume 11
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10.3390/cancers11121904
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Article

Potent Antitumor Activity of Liposomal Irinotecan in an Organoid- and CRISPR-Cas9-Based Murine Model of Gallbladder Cancer

by
Zulrahman Erlangga
1,
Katharina Wolff
1,
Tanja Poth
2,
Alexander Peltzer
3,
Sven Nahnsen
3,
Steffi Spielberg
1,
Kai Timrott
4,
Norman Woller
1,
Florian Kühnel
1,
Michael P. Manns
1,
Anna Saborowski
1,
Arndt Vogel
1,* and
Michael Saborowski
1,*
1
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
2
Department of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
3
Quantitative Biology Center (QBiC), Eberhard Karls Universität Tübingen, 72074 Tübingen, Germany
4
Department of General-, Visceral and Transplantation Surgery, Hannover Medical School, 30625 Hannover, Germany
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(12), 1904; https://doi.org/10.3390/cancers11121904
Submission received: 30 August 2019 / Revised: 23 November 2019 / Accepted: 26 November 2019 / Published: 29 November 2019
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Abstract

Gallbladder cancer is associated with a dismal prognosis, and accurate in vivo models will be elemental to improve our understanding of this deadly disease and develop better treatment options. We have generated a transplantation-based murine model for gallbladder cancer that histologically mimics the human disease, including the development of distant metastasis. Murine gallbladder–derived organoids are genetically modified by either retroviral transduction or transfection with CRISPR/Cas9 encoding plasmids, thereby allowing the rapid generation of complex cancer genotypes. We characterize the model in the presence of two of the most frequent oncogenic drivers—Kras and ERBB2—and provide evidence that the tumor histology is highly dependent on the driver oncogene. Further, we demonstrate the utility of the model for the preclinical assessment of novel therapeutic approaches by showing that liposomal Irinotecan (Nal-IRI) is retained in tumor cells and significantly prolongs the survival of gallbladder cancer–bearing mice compared to conventional irinotecan.
Keywords: organoids; gallbladder; CRISPR/Cas9; Nal-IRI; mouse model organoids; gallbladder; CRISPR/Cas9; Nal-IRI; mouse model

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MDPI and ACS Style

Erlangga, Z.; Wolff, K.; Poth, T.; Peltzer, A.; Nahnsen, S.; Spielberg, S.; Timrott, K.; Woller, N.; Kühnel, F.; Manns, M.P.; et al. Potent Antitumor Activity of Liposomal Irinotecan in an Organoid- and CRISPR-Cas9-Based Murine Model of Gallbladder Cancer. Cancers 2019, 11, 1904. https://doi.org/10.3390/cancers11121904

AMA Style

Erlangga Z, Wolff K, Poth T, Peltzer A, Nahnsen S, Spielberg S, Timrott K, Woller N, Kühnel F, Manns MP, et al. Potent Antitumor Activity of Liposomal Irinotecan in an Organoid- and CRISPR-Cas9-Based Murine Model of Gallbladder Cancer. Cancers. 2019; 11(12):1904. https://doi.org/10.3390/cancers11121904

Chicago/Turabian Style

Erlangga, Zulrahman, Katharina Wolff, Tanja Poth, Alexander Peltzer, Sven Nahnsen, Steffi Spielberg, Kai Timrott, Norman Woller, Florian Kühnel, Michael P. Manns, and et al. 2019. "Potent Antitumor Activity of Liposomal Irinotecan in an Organoid- and CRISPR-Cas9-Based Murine Model of Gallbladder Cancer" Cancers 11, no. 12: 1904. https://doi.org/10.3390/cancers11121904

APA Style

Erlangga, Z., Wolff, K., Poth, T., Peltzer, A., Nahnsen, S., Spielberg, S., Timrott, K., Woller, N., Kühnel, F., Manns, M. P., Saborowski, A., Vogel, A., & Saborowski, M. (2019). Potent Antitumor Activity of Liposomal Irinotecan in an Organoid- and CRISPR-Cas9-Based Murine Model of Gallbladder Cancer. Cancers, 11(12), 1904. https://doi.org/10.3390/cancers11121904

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