Background:Pancreatic neuroendocrine neoplasia (PanNEN) comprises a spectrum, from well-differentiated (i.e., G1, G2) pancreatic neuroendocrine tumors (PanNETs) to poorly differentiated carcinomas (PanNECs). Therapeutic progress is limited by the lack of representative preclinical models. Patient-derived organoids (PDOs) offer potential as translational models, but evidence remains scattered.Methods:We conducted a systematic review of PubMed (Jan 2009–Aug 2025) for original studies reporting on PDOs from PanNEN patients. Eligible studies were screened using the Rayyan software and data extracted from PDO take rates, validation methods, and clinical applications.Results:Twelve studies were included for qualitative and quantitative analyses. PDOs were successfully generated from both PanNETs (G1–G3;n= 26) and PanNECs (n= 6), primarily derived from primary tumors, but several studies also included metastatic sites. Take rates ranged from 33% to 100%, for a cumulative 33 PDOs from 44 attempts (overall take rate: 75%). Validation consistently employed histology, immunohistochemistry, and molecular profiling, with several studies incorporating xenotransplantation or omics approaches. PDOs demonstrated variable culture durations, from short-term (<3 weeks) to long-term (>20 passages). Drug screening studies (n= 7) revealed heterogenous responses to standard agents and pathways (everolimus, sunitinib, and temozolomide) and identified novel vulnerabilities, including EZH2 dependency, PI3K/CDK4/6 synergy, and Bcl-2-linked sensitivities in PanNECs. One study provided evidence of concordance between PDO drug sensitivity and patient responses.Conclusions:Research into PanNEN organoids remains limited. However, PDOs can preserve key histological and molecular features, enable pharmacotyping, and uncover candidate biomarkers for therapy. Despite feasibility across subtypes, progress is constrained by variability in culture success. Standardization and prospective validation are essential to advance PDOs as tools for personalized medicine in PanNENs.
背景：胰腺神经内分泌肿瘤（PanNEN）涵盖从高分化（即G1、G2级）胰腺神经内分泌瘤（PanNETs）到低分化神经内分泌癌（PanNECs）的疾病谱系。由于缺乏具有代表性的临床前模型，其治疗进展受到限制。患者来源类器官（PDOs）具有作为转化模型的潜力，但相关证据仍较为零散。 方法：我们系统检索了PubMed数据库（2009年1月至2025年8月）中报道PanNEN患者PDOs的原始研究。通过Rayyan软件筛选符合条件的研究，并从PDO培养成功率、验证方法和临床应用等方面提取数据。 结果：共纳入12项研究进行定性和定量分析。研究成功从PanNETs（G1-G3级；n=26）和PanNECs（n=6）中培养出PDOs，主要来源于原发肿瘤，但部分研究也纳入了转移灶样本。培养成功率在33%至100%之间，44次培养尝试共获得33个PDOs（总成功率：75%）。验证方法普遍采用组织学、免疫组化和分子谱分析，部分研究结合了异种移植或组学技术。PDOs的培养持续时间存在差异，从短期（<3周）到长期（>20代）不等。药物筛选研究（n=7）显示其对标准药物及通路（依维莫司、舒尼替尼和替莫唑胺）存在异质性反应，并发现了新的治疗靶点，包括PanNECs中EZH2依赖性、PI3K/CDK4/6协同作用及Bcl-2相关敏感性。一项研究证实了PDOs药物敏感性与患者临床反应的一致性。 结论：目前针对PanNEN类器官的研究仍有限。然而，PDOs能够保留关键组织学和分子特征，实现药物表型分析，并发现潜在的治疗生物标志物。尽管各亚型均具备培养可行性，但培养成功率的差异制约了研究进展。标准化流程和前瞻性验证对于推动PDOs成为PanNEN个体化医疗工具至关重要。
肿瘤(癌症)患者之家