Potent antitumor activity of liposomal irinotecan in an organoid- and CRISPR-Cas9-based murine model of gallbladder cancer
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 t...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 November 2019
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| In: |
Cancers
Year: 2019, Volume: 11, Issue: 12 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers11121904 |
| Online Access: | Verlag, Volltext: https://doi.org/10.3390/cancers11121904 Verlag: https://www.mdpi.com/2072-6694/11/12/1904 
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| Author Notes: | Zulrahman Erlangga, Katharina Wolff, Tanja Poth, Alexander Peltzer, Sven Nahnsen, Steffi Spielberg, Kai Timrott, Norman Woller, Florian Kühnel, Michael P. Manns, Anna Saborowski, Arndt Vogel and Michael Saborowski |
| Summary: | 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. |
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| Item Description: | Gesehen am 17.02.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers11121904 |