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Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancer
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. BioReper AB, Linkoping, Sweden.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
BioReper AB, Linkoping, Sweden.
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2024 (English)In: npj Precision Oncology, E-ISSN 2397-768X, Vol. 8, no 1, article id 53Article in journal (Refereed) Published
Abstract [en]

Epithelial ovarian cancer (EOC) is the gynaecological malignancy with highest mortality. Although adjuvant treatment with carboplatin and paclitaxel leads to an objective response in similar to 80% of these patients, a majority will relapse within two years. Better methods for assessing long-term treatment outcomes are needed. To address this, we established safe and efficacious doses of carboplatin and paclitaxel using IGROV-1 zebrafish-CDX models. Then fluorescently-labelled cell suspensions from 83 tumour biopsies collected at exploratory laparotomy of women with suspected EOC were generated and 37 (45%) were successfully implanted in zebrafish larvae. Among these 19 of 27 pathology-confirmed EOC samples (70%) engrafted. These zebrafish patient-derived tumour xenograft (ZTX) models were treated with carboplatin or paclitaxel and tumour growth/regression and metastatic dissemination were recorded. In a subgroup of nine patients, four ZTX models regressed during carboplatin treatment. All four corresponding patients had > 24 months PFS. Furthermore, both ZTX models established from two patients having < 24 months PFS failed to regress during carboplatin treatment. Seven of eight models seeding < 6 metastatic cells were established from patients having > 24 months PFS. In eleven of fourteen patients, FIGO stage I + II or III tumours gave rise to ZTX models seeding < 4 or > 4 metastatic cells, respectively. In conclusion, ZTX models predicted patients having > 24 or < 24 months PFS, based on response/no response to carboplatin. Furthermore, high metastatic dissemination in ZTX models correlated to shorter PFS and more advanced disease at diagnosis. These preliminary results suggest that ZTX models could become a useful prognostic tool in EOC treatment planning.

Place, publisher, year, edition, pages
NATURE PORTFOLIO , 2024. Vol. 8, no 1, article id 53
National Category
Urology and Nephrology
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URN: urn:nbn:se:liu:diva-201678DOI: 10.1038/s41698-024-00550-9ISI: 001176665600001PubMedID: 38413842OAI: oai:DiVA.org:liu-201678DiVA, id: diva2:1845277
Note

Funding Agencies|VINNOVA (Swedish Governmental Agency for Innovation Systems) [2017-01444, H2020-MSCA-RISE-Crystal3, LIO-934261]; VINNOVA

Available from: 2024-03-18 Created: 2024-03-18 Last updated: 2024-03-18

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Lindahl, GabrielFjellander, SebastianSelvaraj, KarthikAbrahamsson, AnnelieRydmark Kersley, AsaFahlgren, AnnaKjölhede, PrebenLinder, StigDabrosin, CharlottaJensen, Lasse
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of OncologyDivision of Diagnostics and Specialist MedicineDivision of Clinical Chemistry and PharmacologyDivision of Children's and Women's HealthForum ÖstergötlandDepartment of Gynaecology and Obstetrics in LinköpingDivision of Cell BiologyDepartment of Clinical Pharmacology
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