State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.

IF 5.4 2区 医学 Q1 IMMUNOLOGY
BioDrugs Pub Date : 2025-03-01 Epub Date: 2025-01-18 DOI:10.1007/s40259-024-00702-0
Julien Giron-Michel, Maël Padelli, Estelle Oberlin, Hind Guenou, Jean-Charles Duclos-Vallée
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Abstract

Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment. These modifications enable CSCs to exhibit plasticity, differentiating into various resistant tumor cell types. Addressing this challenge requires urgent efforts to develop personalized treatments guided by biomarkers, with a specific focus on targeting CSCs. The lack of effective precision treatments for PLCs is partly due to the scarcity of ex vivo preclinical models that accurately capture the complexity of CSC-related tumors and can predict therapeutic responses. Fortunately, recent advancements in the establishment of patient-derived liver cancer cell lines and organoids have opened new avenues for precision medicine research. Notably, patient-derived organoid (PDO) cultures have demonstrated self-assembly and self-renewal capabilities, retaining essential characteristics of their respective in vivo tissues, including both inter- and intratumoral heterogeneities. The emergence of PDOs derived from PLCs serves as patient avatars, enabling preclinical investigations for patient stratification, screening of anticancer drugs, efficacy testing, and thereby advancing the field of precision medicine. This review offers a comprehensive summary of the advancements in constructing PLC-derived PDO models. Emphasis is placed on the role of CSCs, which not only contribute significantly to the establishment of PDO cultures but also faithfully capture tumor heterogeneity and the ensuing development of therapy resistance. The exploration of PDOs' benefits in personalized medicine research is undertaken, including a discussion of their limitations, particularly in terms of culture conditions, reproducibility, and scalability.

最先进的肝癌类器官:为个性化治疗建模癌症干细胞异质性。
肝癌是一个全球性的健康挑战,治疗选择有限。值得注意的是,目前治疗原发性肝癌(plc)患者的有限成功可能归因于肝细胞癌(hcc)和肝内胆管癌(iCCAs)的高度异质性。这种异质性随着肿瘤起始干细胞或癌症干细胞(CSCs)经历(epi)遗传改变或在肿瘤微环境中遇到微环境变化而演变。这些修饰使csc表现出可塑性,分化为各种耐药肿瘤细胞类型。应对这一挑战需要迫切努力开发以生物标志物为指导的个性化治疗,并特别关注针对csc的治疗。plc缺乏有效的精确治疗,部分原因是缺乏准确捕获csc相关肿瘤复杂性并可以预测治疗反应的体外临床前模型。幸运的是,最近在建立患者来源的肝癌细胞系和类器官方面取得的进展为精准医学研究开辟了新的途径。值得注意的是,患者源性类器官(PDO)培养物显示出了自我组装和自我更新的能力,保留了各自体内组织的基本特征,包括肿瘤间和肿瘤内的异质性。从plc衍生的pdo的出现可以作为患者的化身,使临床前研究能够进行患者分层,筛选抗癌药物,功效测试,从而推进精准医学领域。本文综述了构建plc衍生PDO模型的进展。重点放在CSCs的作用上,它不仅对PDO培养的建立有重要贡献,而且还忠实地捕捉肿瘤异质性和随后的治疗耐药性的发展。探索pdo在个体化医学研究中的益处,包括对其局限性的讨论,特别是在培养条件、可重复性和可扩展性方面。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BioDrugs
BioDrugs 医学-免疫学
CiteScore
12.60
自引率
2.90%
发文量
50
审稿时长
>12 weeks
期刊介绍: An essential resource for R&D professionals and clinicians with an interest in biologic therapies. BioDrugs covers the development and therapeutic application of biotechnology-based pharmaceuticals and diagnostic products for the treatment of human disease. BioDrugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.
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