Yildiz Merve, Romano Andrea, Xanthoulea Sofia
GROW-Research Institute for Oncology & Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands.
Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, 6229 HX Maastricht, The Netherlands.
Cancers (Basel). 2024 Nov 28;16(23):3994. doi: 10.3390/cancers16233994.
Murine xenograft models are valuable and increasingly used preclinical tools in cancer research to understand disease pathogenesis and guide treatment options. The aim of this narrative review is to summarize the studies that employed mouse xenograft models, using cell lines, patient-derived tumors, or organoids, in endometrial cancer (EC) research, detailing their methodology and main findings. We identified 27 articles reporting on heterotopic EC xenografts, including subcutaneous, subrenal capsule, intraperitoneal, and retro-orbital models, and 18 articles using orthotopic xenografts. Subcutaneous xenografts generated using either cell lines or patient tumors have been widely used; however, their low engraftment rates and the inability to recapitulate main clinical features such as metastases limit their translational value. Subrenal capsule models showed improved engraftment rates compared to subcutaneous models, but tumors exhibited slower and constrained tumor growth. Orthotopic models are technically more challenging to generate and monitor, but tumor growth occurs in a relevant microenvironment and EC ortho-xenografts exhibit high engraftment rates and metastases to clinically relevant sites. Cell line-based xenograft (CDX) models are attractive tools because they are convenient, easy to use, and amenable to genetic modifications, making them suitable for proof-of-concept approaches and large-scale studies. EC xenografts developed from patient tumors (PDTXs) are more labor/cost-intensive for their establishment but can capture the genetic and molecular heterogeneity within and across histologic subtypes and can inform personalized patient treatment. EC organoid-based xenograft (PDOX) models combine the advantages of both CDXs and PDTXs since they are more time- and cost-effective, faithfully maintain tumor characteristics and therapeutic responses, and can be genetically modified. Despite substantial progress in EC management, there are still several unmet needs. Efficient targeted treatments are currently indicated only for a small subgroup of patients, while women with recurrent or advanced-stage EC have very few therapeutic options and their prognosis remains unfavorable. Novel (targeted) drugs, combinational regimens and tools to predict the real drug response in patients are urgently needed. Xenograft models are expected to inform about disease mechanisms and to help identify novel therapeutic options and suitable target patients.
小鼠异种移植模型是癌症研究中宝贵且使用日益广泛的临床前工具，用于了解疾病发病机制并指导治疗方案的选择。本叙述性综述的目的是总结在子宫内膜癌（EC）研究中使用小鼠异种移植模型（使用细胞系、患者来源的肿瘤或类器官）的研究，详细介绍其方法和主要发现。我们鉴定出27篇报道异位EC异种移植的文章，包括皮下、肾包膜下、腹腔内和眶后模型，以及18篇使用原位异种移植的文章。使用细胞系或患者肿瘤生成的皮下异种移植已被广泛应用；然而，它们的低植入率以及无法重现转移等主要临床特征限制了其转化价值。与皮下模型相比，肾包膜下模型显示出更高的植入率，但肿瘤生长较慢且受限。原位模型在生成和监测方面技术上更具挑战性，但肿瘤在相关微环境中生长，并且EC原位异种移植显示出高植入率以及向临床相关部位的转移。基于细胞系的异种移植（CDX）模型是有吸引力的工具，因为它们方便、易于使用且适合基因改造，使其适用于概念验证方法和大规模研究。由患者肿瘤（PDTXs）开发的EC异种移植在建立过程中劳动强度/成本更高，但可以捕捉组织学亚型内部和之间的遗传和分子异质性，并可为个性化患者治疗提供信息。基于EC类器官的异种移植（PDOX）模型结合了CDXs和PDTXs的优点，因为它们更节省时间和成本，忠实地维持肿瘤特征和治疗反应，并且可以进行基因改造。尽管在EC治疗方面取得了重大进展，但仍有一些未满足的需求。目前高效的靶向治疗仅适用于一小部分患者，而复发或晚期EC的女性治疗选择非常少，其预后仍然不佳。迫切需要新型（靶向）药物、联合治疗方案以及预测患者真实药物反应的工具。异种移植模型有望阐明疾病机制，并有助于确定新型治疗选择和合适的目标患者。
