Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models
Mucinous peritoneal metastases (PM) generally respond poorly to systemic treatment, and there is a clear unmet need for new treatment strategies to improve survival and quality of life for patients with PM. In this work, the growth inhibitory effect of five drugs (oxaliplatin (OXA; 5 mg/kg), irinote...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-08-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523320302977 |
| _version_ | 1818959519906004992 |
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| author | Karianne Giller Fleten Christin Lund-Andersen Stein Waagene Torveig Weum Abrahamsen Yrr Mørch Kjetil Boye Annette Torgunrud Kjersti Flatmark |
| author_facet | Karianne Giller Fleten Christin Lund-Andersen Stein Waagene Torveig Weum Abrahamsen Yrr Mørch Kjetil Boye Annette Torgunrud Kjersti Flatmark |
| author_sort | Karianne Giller Fleten |
| collection | DOAJ |
| description | Mucinous peritoneal metastases (PM) generally respond poorly to systemic treatment, and there is a clear unmet need for new treatment strategies to improve survival and quality of life for patients with PM. In this work, the growth inhibitory effect of five drugs (oxaliplatin (OXA; 5 mg/kg), irinotecan (IRI; 60 mg/kg), cabazitaxel (CBZ; 15 or 30 mg/kg), regorafenib (REG; 10, 30 or 60 mg/kg), and capecitabine (CAP; 359 or 755 mg/kg) was investigated in three orthotopic patient-derived xenograft models that mimic mucinous PM.Drugs were administered intraperitoneally (i.p.) as monotherapy weekly for 4 weeks (OXA, IRI), as one single i.p. injection (CBZ), or orally (REG, CAP) daily 5 of 7 days per week for four weeks, and i.p. tumor growth and survival were monitored and compared between treatment groups. The i.p. administered drugs (OXA, IRI, CBZ) had the strongest growth inhibitory effect, with OXA being most efficacious, completely inhibiting tumor growth in the majority of the animals. CBZ and IRI also strongly inhibited tumor growth, but with more variation in efficacy between the models. A moderate reduction in tumor growth was observed in all models treated with REG, while CAP had little to no growth inhibitory effect. Targeted next-generation-sequencing has identified mutational profiles typically associated with PM (mutations in KRAS, GNAS, and BRAF oncogenes), supporting the representativeness of the models. The results presented in this work support the continued exploration of i.p. treatment protocols for PM, with OXA remaining and CBZ emerging as particularly interesting candidates for further studies. |
| first_indexed | 2024-12-20T11:42:56Z |
| format | Article |
| id | doaj.art-c664c599f0e54faea0f890aa18ffc530 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-20T11:42:56Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-c664c599f0e54faea0f890aa18ffc5302022-12-21T19:41:57ZengElsevierTranslational Oncology1936-52332020-08-01138100793Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft ModelsKarianne Giller Fleten0Christin Lund-Andersen1Stein Waagene2Torveig Weum Abrahamsen3Yrr Mørch4Kjetil Boye5Annette Torgunrud6Kjersti Flatmark7Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, NorwayDepartment of Biotechnology and Nanomedicine, SINTEF, AS, Trondheim, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Address all correspondence to: Kjersti Flatmark, Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310, Oslo, Norway.Mucinous peritoneal metastases (PM) generally respond poorly to systemic treatment, and there is a clear unmet need for new treatment strategies to improve survival and quality of life for patients with PM. In this work, the growth inhibitory effect of five drugs (oxaliplatin (OXA; 5 mg/kg), irinotecan (IRI; 60 mg/kg), cabazitaxel (CBZ; 15 or 30 mg/kg), regorafenib (REG; 10, 30 or 60 mg/kg), and capecitabine (CAP; 359 or 755 mg/kg) was investigated in three orthotopic patient-derived xenograft models that mimic mucinous PM.Drugs were administered intraperitoneally (i.p.) as monotherapy weekly for 4 weeks (OXA, IRI), as one single i.p. injection (CBZ), or orally (REG, CAP) daily 5 of 7 days per week for four weeks, and i.p. tumor growth and survival were monitored and compared between treatment groups. The i.p. administered drugs (OXA, IRI, CBZ) had the strongest growth inhibitory effect, with OXA being most efficacious, completely inhibiting tumor growth in the majority of the animals. CBZ and IRI also strongly inhibited tumor growth, but with more variation in efficacy between the models. A moderate reduction in tumor growth was observed in all models treated with REG, while CAP had little to no growth inhibitory effect. Targeted next-generation-sequencing has identified mutational profiles typically associated with PM (mutations in KRAS, GNAS, and BRAF oncogenes), supporting the representativeness of the models. The results presented in this work support the continued exploration of i.p. treatment protocols for PM, with OXA remaining and CBZ emerging as particularly interesting candidates for further studies.http://www.sciencedirect.com/science/article/pii/S1936523320302977 |
| spellingShingle | Karianne Giller Fleten Christin Lund-Andersen Stein Waagene Torveig Weum Abrahamsen Yrr Mørch Kjetil Boye Annette Torgunrud Kjersti Flatmark Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models Translational Oncology |
| title | Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models |
| title_full | Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models |
| title_fullStr | Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models |
| title_full_unstemmed | Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models |
| title_short | Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models |
| title_sort | experimental treatment of mucinous peritoneal metastases using patient derived xenograft models |
| url | http://www.sciencedirect.com/science/article/pii/S1936523320302977 |
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