Supplementary Material for: Models of Gastroenteropancreatic Neuroendocrine Neoplasms: Current Status and Future Directions

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a rare, heterogeneous group of tumors that originate from the endocrine system of the gastrointestinal tract and pancreas. GEP-NENs are subdivided according to their differentiation into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Since GEP-NENs represent rare diseases, only limited data from large prospective, randomized clinical trials are available, and recommendations for treatment of GEP-NEN are in part based on data from retrospective analyses or case series. In this context, tractable disease models that reflect the situation in humans and that allow to recapitulate the different clinical aspects and disease stages of GEP-NET or GEP-NEC are urgently needed. In this review, we highlight available data on mouse models for GEP-NEN. We discuss how these models reflect tumor biology of human disease and whether these models could serve as a tool for understanding the pathogenesis of GEP-NEN and for disease modeling and pharmacosensitivity assays, facilitating prediction of treatment response in patients. In addition, open issues applicable for future developments will be discussed.

胃肠胰神经内分泌肿瘤（Gastroenteropancreatic neuroendocrine neoplasms, GEP-NENs）是一类起源于胃肠道及胰腺内分泌系统的罕见异质性肿瘤。根据分化程度，GEP-NENs可分为高分化神经内分泌肿瘤（Neuroendocrine tumors, NETs）与低分化神经内分泌癌（Neuroendocrine carcinomas, NECs）。由于GEP-NENs属于罕见病，目前来自大规模前瞻性随机临床试验的可用数据十分有限，GEP-NEN的治疗推荐部分基于回顾性分析或病例系列研究数据。在此背景下，亟需能够模拟人体真实病理状态、可复现GEP-NET或GEP-NEC不同临床特征与疾病分期的可操作疾病模型。本综述梳理当前已公开的GEP-NEN小鼠模型相关研究数据，探讨这些模型对人类肿瘤生物学特征的复刻程度，以及其能否作为研究GEP-NEN发病机制、开展疾病建模与药物敏感性实验的工具，从而助力患者治疗响应的预测。此外，本文还将探讨该领域未来发展尚存的开放性问题。