@article{01J08XBH264AJJFMPD22RZKEG7,
  abstract     = {{Simple Summary: Selecting and developing effective therapies for distinct epithelial ovarian cancer subtypes necessitates tumor models that accurately recapitulate the individual characteristics and microenvironmental interactions. Patient-derived tumor models offer a promising approach by preserving the tumor's integrity, providing a platform for personalized treatment strategies. Zebrafish embryos could be a useful tool for quickly testing potential treatments in parallel. In this research article, we aimed to evaluate the model using a real-world case study and compare results with existing in vitro and in vivo models. A patient-derived cell line from a low-grade serous ovarian cancer with a KRAS mutation was engrafted in zebrafish embryos. Xenografts were assigned to a five-day treatment with trametinib and/or luminespib, targeting two complementary pathways that have previously shown efficacy in other cancer models of this cell line. The zebrafish model offers several options to analyze the response of the tumor to drug exposure. Here, we evaluated both cell growth and cell death, which showed a significant positive tumor response upon treatment that was amplified further by combining the drugs. 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.}},
  articleno    = {{1812}},
  author       = {{Fieuws, Charlotte and Bek, Jan Willem and Parton, Bram and De Neef, Elyne and De Wever, Olivier and Hoorne, Milena and Estrada, Marta F. and Van Dorpe, Jo and Denys, Hannelore and Van de Vijver, Koen and Claes, Kathleen}},
  issn         = {{2072-6694}},
  journal      = {{CANCERS}},
  keywords     = {{ovarian cancer,zebrafish xenografts,functional precision medicine,zAvatars,low-grade serous,EXPRESSION,XENOGRAFT}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{13}},
  title        = {{Zebrafish avatars : toward functional precision medicine in low-grade serous ovarian cancer}},
  url          = {{http://doi.org/10.3390/cancers16101812}},
  volume       = {{16}},
  year         = {{2024}},
}

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