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Zebrafish Avatars: Toward Functional Precision Medicine in Low-Grade Serous Ovarian Cancer.
Fieuws, Charlotte; Bek, Jan Willem; Parton, Bram; De Neef, Elyne; De Wever, Olivier; Hoorne, Milena; Estrada, Marta F; Van Dorpe, Jo; Denys, Hannelore; Van de Vijver, Koen; Claes, Kathleen B M.
Afiliación
  • Fieuws C; Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium.
  • Bek JW; Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium.
  • Parton B; Cancer Research Institute Ghent, 9000 Ghent, Belgium.
  • De Neef E; Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium.
  • De Wever O; Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium.
  • Hoorne M; Cancer Research Institute Ghent, 9000 Ghent, Belgium.
  • Estrada MF; Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium.
  • Van Dorpe J; Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium.
  • Denys H; Cancer Research Institute Ghent, 9000 Ghent, Belgium.
  • Van de Vijver K; Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium.
  • Claes KBM; Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium.
Cancers (Basel) ; 16(10)2024 May 09.
Article en En | MEDLINE | ID: mdl-38791891
ABSTRACT
Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines and 3D tumor models. To address this goal, a well-characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G>T (p.(Gly12Val)) was used. Fluorescently labeled tumor cells were injected into the perivitelline space of 2 days' post-fertilization zebrafish embryos. At 1 day post-injection, xenografts were assessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib and trametinib + luminespib. Subsequently, xenografts were euthanized and analyzed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n = 84) in vivo, with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC.
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Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2024 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2024 Tipo del documento: Article