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上皮性卵巢癌的临床前模型:实际考虑因素及有意义应用的挑战。

Preclinical models of epithelial ovarian cancer: practical considerations and challenges for a meaningful application.

机构信息

Unità di Medicina Traslazionale per la Salute della Donna e del Bambino, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.

Dipartimento Universitario Scienze della Vita e Sanità Pubblica-Sezione di Ginecologia ed Ostetricia - Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy.

出版信息

Cell Mol Life Sci. 2022 Jun 16;79(7):364. doi: 10.1007/s00018-022-04395-y.

DOI:10.1007/s00018-022-04395-y
PMID:35705879
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9200670/
Abstract

Despite many improvements in ovarian cancer diagnosis and treatment, until now, conventional chemotherapy and new biological drugs have not been shown to cure the disease, and the overall prognosis remains poor. Over 90% of ovarian malignancies are categorized as epithelial ovarian cancers (EOC), a collection of different types of neoplasms with distinctive disease biology, response to chemotherapy, and outcome. Advances in our understanding of the histopathology and molecular features of EOC subtypes, as well as the cellular origins of these cancers, have given a boost to the development of clinically relevant experimental models. The overall goal of this review is to provide a comprehensive description of the available preclinical investigational approaches aimed at better characterizing disease development and progression and at identifying new therapeutic strategies. Systems discussed comprise monolayer (2D) and three-dimensional (3D) cultures of established and primary cancer cell lines, organoids and patient-derived explants, animal models, including carcinogen-induced, syngeneic, genetically engineered mouse, xenografts, patient-derived xenografts (PDX), humanized PDX, and the zebrafish and the laying hen models. Recent advances in tumour-on-a-chip platforms are also detailed. The critical analysis of strengths and weaknesses of each experimental model will aid in identifying opportunities to optimize their translational value.

摘要

尽管在卵巢癌的诊断和治疗方面取得了许多进展,但到目前为止,常规化疗和新型生物药物并未显示出能够治愈该疾病,整体预后仍然较差。超过 90%的卵巢恶性肿瘤被归类为上皮性卵巢癌(EOC),这是一组具有不同类型肿瘤的集合,其疾病生物学、对化疗的反应和结局都有明显的不同。我们对 EOC 亚型的组织病理学和分子特征以及这些癌症的细胞起源的理解的进步,为开发具有临床相关性的实验模型提供了助力。本综述的总体目标是全面描述现有的临床前研究方法,旨在更好地描述疾病的发展和进展,并确定新的治疗策略。所讨论的系统包括已建立的和原代癌细胞系的单层(2D)和三维(3D)培养、类器官和患者来源的外植体、动物模型,包括致癌物诱导的、同基因的、基因工程小鼠、异种移植、患者来源的异种移植(PDX)、人源化 PDX 以及斑马鱼和蛋鸡模型。肿瘤芯片平台的最新进展也有详细描述。对每种实验模型的优缺点进行批判性分析,有助于确定优化其转化价值的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1413/11072439/d74df2136260/18_2022_4395_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1413/11072439/e7a95525b27f/18_2022_4395_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1413/11072439/5b0be630fd68/18_2022_4395_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1413/11072439/d74df2136260/18_2022_4395_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1413/11072439/e7a95525b27f/18_2022_4395_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1413/11072439/5b0be630fd68/18_2022_4395_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1413/11072439/d74df2136260/18_2022_4395_Fig3_HTML.jpg

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Identification of a novel gene signature predicting response to first-line chemotherapy in BRCA wild-type high-grade serous ovarian cancer patients.鉴定一种新的基因特征,可预测 BRCA 野生型高级别浆液性卵巢癌患者对一线化疗的反应。
J Exp Clin Cancer Res. 2022 Feb 4;41(1):50. doi: 10.1186/s13046-022-02265-w.
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Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer.
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Biochem Biophys Rep. 2024 Oct 17;40:101838. doi: 10.1016/j.bbrep.2024.101838. eCollection 2024 Dec.
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Ovarian cancer cells exhibit diverse migration strategies on stiff collagenous substrata.卵巢癌细胞在硬胶原质基底上表现出多样化的迁移策略。
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Targeted radiopharmaceuticals: an underexplored strategy for ovarian cancer.靶向放射性药物:卵巢癌研究不足的策略。
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