Department of Pathology, UT Southwestern Medical Center, 5909 Harry Hines Boulevard, Dallas, TX 75390-9234, USA.
Curr Mol Med. 2013 Mar;13(3):333-9.
Pancreatic neuroendocrine tumors (PNETs) are rare but are well understood to cover a broad spectrum of clinical presentation, tumor biology and prognosis. More than 60% of PNETs are diagnosed at advanced disease stage and are ineligible for surgical resection. Prior to 2011, streptozocin was the only approved agent for unresectable advanced PNETs. In recent years, breakthroughs in signal pathway research have led to the identification of new therapeutic targets and agents directed at the molecular level. In 2011, two new targeted therapeutic agents, sunitinib and everolimus, were approved by the Food and Drug Administration (FDA). Sunitinib is an inhibitor of multiple tyrosine kinases, and everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) pathway. This review discusses the major signaling pathways that are frequently mutated or deregulated in PNETs, and the implications of molecular alterations for PNET therapy. Biologic therapy through targeting relevant pathways represents a promising approach in the therapy of advanced and unresectable PNETs.
胰腺神经内分泌肿瘤（PNETs）较为罕见，但具有广泛的临床表现、肿瘤生物学和预后异质性。超过 60%的 PNETs 在疾病晚期被诊断，且不符合手术切除的条件。在 2011 年之前，链脲佐菌素是唯一被批准用于不可切除的晚期 PNETs 的药物。近年来，信号通路研究的突破导致了新的治疗靶点和针对分子水平的药物的鉴定。2011 年，两种新的靶向治疗药物，舒尼替尼和依维莫司，被美国食品和药物管理局（FDA）批准。舒尼替尼是一种多靶点酪氨酸激酶抑制剂，依维莫司是一种哺乳动物雷帕霉素靶蛋白（mTOR）通路抑制剂。本文综述了 PNETs 中经常发生突变或失调控的主要信号通路，以及分子改变对 PNET 治疗的影响。通过针对相关通路的生物治疗代表了治疗晚期和不可切除的 PNETs 的一种有前途的方法。
