University Hospital of Bonn, Center of Integrated Oncology Cologne-Bonn, Department of Internal Medicine 3, Biomedizinisches Zentrum, Room 3G 024, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany.
Expert Opin Pharmacother. 2012 Oct;13(14):2073-84. doi: 10.1517/14656566.2012.713348. Epub 2012 Aug 8.
Pancreatic neuroendocrine tumors (PNET) represent the second most common primary malignancy of the pancreas. Until recently, therapeutic options for advanced PNET have been limited.
A recently published Phase III clinical trial demonstrated striking therapeutic activity of the mTOR inhibitor everolimus in advanced PNET and led to its approval for this indication by the FDA. This review discusses this landmark discovery in the context of currently available therapeutic options, pathophysiology and molecular genetics of PNET.
The approval of everolimus for the treatment of PNET marks a major step forward in the clinical management of this disease and represents a notable example of the successful translation of a targeted therapy that was initially developed based on findings at the lab bench, into everyday clinical practice. These results encourage hopes that the overall therapeutic efficacy of such approaches can be further enhanced by the introduction of combinatorial regimens, simultaneously targeting more than one oncogenic signaling pathway, as well as by stratification of patients based on the individual genetic setup of their tumors.
胰腺神经内分泌肿瘤（PNET）是胰腺的第二大常见原发性恶性肿瘤。直到最近，晚期 PNET 的治疗选择还很有限。
最近发表的一项 III 期临床试验表明，mTOR 抑制剂依维莫司在晚期 PNET 中具有显著的治疗活性，并因此获得 FDA 批准用于该适应证。这篇综述讨论了这一具有里程碑意义的发现，包括目前可用的治疗选择、PNET 的病理生理学和分子遗传学。
依维莫司被批准用于治疗 PNET，这是该疾病临床管理的重大进展，也是一个成功的例子，说明了最初基于实验室发现开发的靶向治疗如何成功转化为日常临床实践。这些结果令人鼓舞地希望，通过引入同时针对多个致癌信号通路的联合治疗方案，以及根据肿瘤的个体基因结构对患者进行分层，可以进一步提高此类方法的总体治疗效果。
