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 theKRASmutation 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.
卵巢癌（OC）是影响卵巢的恶性肿瘤的总称，但所有亚型的治疗方案主要来源于最大的亚型——高级别浆液性卵巢癌。“功能性精准医疗”的概念涉及基于患者组织直接暴露于药物的方式，获得关于治疗选择的个性化见解。这对于低级别浆液性卵巢癌（LGSOC）等罕见亚型尤其具有前景。本研究旨在利用斑马鱼胚胎建立LGSOC的体内模型，比较先前在小鼠PDX模型、细胞系和3D肿瘤模型中观察到的治疗反应。为实现这一目标，研究采用了一种特征明确、携带KRAS突变c.35 G>T（p.(Gly12Val)）的患者来源LGSOC细胞系。将荧光标记的肿瘤细胞注射到受精后2天的斑马鱼胚胎卵黄周间隙中。注射后1天，评估异种移植物的肿瘤大小，随后随机分配至曲美替尼、luminespib及曲美替尼+luminespib联合治疗组。之后，对异种移植物实施安乐死，并通过共聚焦显微镜分析其凋亡和增殖情况。肿瘤细胞在体内形成致密肿瘤团块（n=84），并呈现清晰的Ki67染色，表明其具有增殖活性。斑马鱼异种移植物在两周内对曲美替尼和luminespib（单独或联合使用）表现出敏感性，这确立了其作为现有体外和体内模型的快速补充工具，用于评估LGSOC的靶向治疗。
Zebrafish Avatars: Toward Functional Precision Medicine in Low-Grade Serous Ovarian Cancer
肿瘤(癌症)患者之家