Yellapragada Srujana V, Forsythe Steven D, Madigan James P, Sadowski Samira M
Neuroendocrine Cancer Therapy Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Mol Sci. 2025 Jun 12;26(12):5635. doi: 10.3390/ijms26125635.
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a family of tumors that arise throughout the gastrointestinal tract. These tumors are heterogeneous, with complex clinical symptoms and tumor behaviors, and demonstrate rising incidence rates worldwide. In addition to their nature, GEP-NETs possess limited diagnostic and therapeutic options, which results in poor survival rates for patients with metastatic tumors. Given these findings, a further analysis of these tumors' biology is needed to determine new therapeutic strategies. The tumor microenvironment (TME) consists of several residual cell populations and non-cellular components whose altered behavior creates a tumor-supportive niche. Studies from other cancers demonstrate the TME's significance in tumor initiation, progression, and spread. In this review, we discuss efforts to characterize the TME in GEP-NETs. Preliminary studies of the immune system in GEP-NETs have led to several major clinical trials, with limited success. Efforts to target signaling crosstalk between cancer-associated fibroblasts, vascular endothelial cells, and tumor cells has led to major discoveries and multiple approved therapies. Finally, alterations to the extracellular matrix may lead towards an improved understanding of GEP-NET development, behavior, and improved detection methods. While research has rapidly expanded our knowledge within the last decade, further work is needed to bring our understanding of the GEP-NET TME in line with other rare cancers.
胃肠胰神经内分泌肿瘤（GEP-NETs）是一类起源于整个胃肠道的肿瘤。这些肿瘤具有异质性，临床症状和肿瘤行为复杂，且在全球范围内发病率呈上升趋势。除了其本质特征外，GEP-NETs的诊断和治疗选择有限，这导致转移性肿瘤患者的生存率较低。鉴于这些发现，需要进一步分析这些肿瘤的生物学特性以确定新的治疗策略。肿瘤微环境（TME）由几种残留细胞群和非细胞成分组成，其行为改变形成了一个支持肿瘤的微环境。其他癌症的研究表明TME在肿瘤的发生、发展和扩散中具有重要意义。在本综述中，我们讨论了对GEP-NETs中TME进行特征描述的相关研究。对GEP-NETs免疫系统的初步研究已引发了多项主要临床试验，但成效有限。针对癌症相关成纤维细胞、血管内皮细胞和肿瘤细胞之间信号串扰的研究已取得了重大发现并促成了多种获批疗法。最后，细胞外基质的改变可能有助于更好地理解GEP-NETs的发展、行为，并改进检测方法。虽然在过去十年中研究迅速扩展了我们的知识，但仍需要进一步开展工作，以使我们对GEP-NETs肿瘤微环境的理解与其他罕见癌症的研究水平相当。
