Department of Hepatology, Gastroenterology and Endocrinology, Charité Medical School, Berlin, Germany.
Neuroendocrinology. 2011;94(3):177-90. doi: 10.1159/000329386. Epub 2011 Aug 31.
Pancreatic neuroendocrine tumors (pancreatic NET) are relatively rare, slowly growing tumors, although their incidence is increasing, and patients may survive for several years with metastatic disease. Apart from symptomatic relief, there have been few treatment options for these tumors in the past. More recently, investigators have explored the potential of molecularly targeted agents in treating pancreatic NET, with some success. In this review, we consider the data supporting exploitation of different targets in pancreatic NET, including peptide receptors, receptor tyrosine kinases (involved in tumor angiogenesis and more directly supporting tumor growth), and intracellular targets, such as the mammalian target of rapamycin (mTOR), which has a central role in regulating cell growth, metabolism, and apoptosis. Probably due to the paucity of pancreatic NET, many clinical trials to date have included heterogeneous NET populations, and there are few randomized studies of this specific patient population. Very recently, promising results have been achieved in placebo-controlled, phase III trials with the multitargeted tyrosine kinase inhibitor, sunitinib, and the mTOR inhibitor, everolimus. These agents have been approved or are currently being reviewed by authorities for use in patients with pancreatic NET. Here we review potential molecular targets in pancreatic NET and summarize the available data for targeted agents from phase II and III trials open to patients with this tumor.
胰腺神经内分泌肿瘤（pancreatic NET）是相对罕见的、生长缓慢的肿瘤，尽管其发病率在增加，并且转移性疾病患者的存活时间可能长达数年。除了症状缓解外，过去这些肿瘤的治疗选择很少。最近，研究人员探索了在治疗胰腺 NET 中使用分子靶向药物的潜力，取得了一些成功。在这篇综述中，我们考虑了支持在胰腺 NET 中利用不同靶点的数据，包括肽受体、受体酪氨酸激酶（涉及肿瘤血管生成，并更直接地支持肿瘤生长）和细胞内靶点，如雷帕霉素哺乳动物靶标（mTOR），它在调节细胞生长、代谢和细胞凋亡方面起着核心作用。可能由于胰腺 NET 的稀缺性，迄今为止许多临床试验都包括了异质性 NET 人群，并且针对这种特定患者人群的随机研究很少。最近，在安慰剂对照的 III 期临床试验中，多靶点酪氨酸激酶抑制剂舒尼替尼和 mTOR 抑制剂依维莫司取得了有希望的结果。这些药物已被批准或正在被监管机构审查，用于治疗胰腺 NET 患者。在这里，我们综述了胰腺 NET 中的潜在分子靶点，并总结了来自开放给患有这种肿瘤的患者的 II 期和 III 期试验的靶向药物的可用数据。
