Department of Oncology, Yerevan State Medical University, Yerevan, Armenia.
Adult Solid Tumor Chemotherapy Clinic, Professor Yeolan Hematology Center, Yerevan, Armenia.
Cancer. 2021 Feb 1;127(3):345-353. doi: 10.1002/cncr.33354. Epub 2020 Dec 3.
Pancreatic neuroendocrine neoplasms (panNENs) are the second most common epithelial tumors of the pancreas. Despite improvements in prognostic grading and staging systems, it remains a challenge to predict the clinical behavior of panNENs and the response to specific therapies given the high degree of heterogeneity of these tumors. Most panNENs are nonfunctional and present as advanced disease. However, systemic therapies provide modest benefits. Therefore, there is a need for predictive biomarkers to develop personalized treatment and to advance new drug development. The somatostatin receptors remain the only clinically established prognostic and predictive biomarkers in panNENs. Oncogenic drivers are at a very low frequency. Commonly mutated genes in panNENs include MEN1, chromatin remodeling genes (DAXX and ATRX), and mammalian target of rapamycin pathway genes. In contrast, poorly differentiated neuroendocrine carcinomas (panNECs), which carry a very poor prognosis, have distinctive mutations in certain genes (eg, RB1 and p53). Ongoing research to integrate epigenomics will provide tremendous opportunities to improve current understanding of the clinical heterogeneity of pancreatic neuroendocrine tumors and provide invaluable insight into the biology of these tumors, new drug development, and establishing personalized therapies.
胰腺神经内分泌肿瘤（panNENs）是胰腺第二大常见的上皮性肿瘤。尽管在预后分级和分期系统方面有所改进，但由于这些肿瘤具有高度异质性，预测 panNENs 的临床行为和对特定治疗的反应仍然具有挑战性。大多数 panNENs 为无功能性，且处于晚期疾病状态。然而，系统治疗仅能提供适度的益处。因此，需要预测性生物标志物来制定个性化治疗方案并推进新药研发。生长抑素受体仍然是 panNENs 中唯一临床确立的预后和预测性生物标志物。致癌驱动因素的频率非常低。panNENs 中常见的突变基因包括 MEN1、染色质重塑基因（DAXX 和 ATRX）以及哺乳动物雷帕霉素靶蛋白通路基因。相比之下，预后极差的低分化神经内分泌癌（panNECs）在某些基因（如 RB1 和 p53）中具有独特的突变。正在进行的整合表观基因组学的研究将为改善目前对胰腺神经内分泌肿瘤临床异质性的理解提供巨大机会，并为这些肿瘤的生物学、新药研发和建立个性化治疗提供宝贵的见解。
