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用于理解疾病发病机制和指导治疗方案的重要且日益普及的临床前工具。本文旨在系统综述子宫内膜癌研究中采用细胞系、患者来源肿瘤或类器官构建的小鼠异种移植模型的相关文献，详细阐述其研究方法与主要发现。共纳入27篇报道异位移植模型（包括皮下、肾包膜下、腹腔及眶后移植）的研究，以及18篇使用原位移植模型的研究。基于细胞系或患者肿瘤构建的皮下移植模型应用广泛，但其移植成功率较低，且无法重现转移等关键临床特征，限制了其转化价值。肾包膜下模型较皮下模型显示出更高的移植成功率，但肿瘤生长速度较慢且受限。原位移植模型在构建和监测方面技术要求更高，但肿瘤在相关微环境中生长，且子宫内膜癌原位移植模型表现出高移植率及向临床相关部位的转移特性。基于细胞系的异种移植模型因其便捷性、易用性和可遗传修饰特性，成为概念验证和大规模研究的理想工具。患者来源肿瘤移植模型建立过程虽更耗费人力物力，但能准确反映组织学亚型内及亚型间的遗传与分子异质性，为个体化治疗提供依据。基于类器官的移植模型兼具上述两种模型的优势：更具时间与经济效率、能忠实维持肿瘤特征和治疗反应、并具备遗传修饰潜力。尽管子宫内膜癌诊疗已取得显著进展，仍存在诸多未满足的临床需求。当前高效靶向治疗仅适用于少数患者群体，而复发或晚期子宫内膜癌患者的治疗选择极为有限，预后依然不佳。亟需开发新型（靶向）药物、联合治疗方案及预测患者真实药物反应的工具。异种移植模型有望揭示疾病机制，助力发现新型治疗策略并筛选适宜的目标患者群体。
Murine Xenograft Models as Preclinical Tools in Endometrial Cancer Research
肿瘤(癌症)患者之家