胰腺癌抗血管生成治疗的研究现状和进展

Research status and progression in anti-angiogenesis therapy for pancreatic cancer

随着抗血管生成类药物研发的进步,抗血管生成治疗也成为胰腺癌治疗领域中的研究热点。目前抗血管生成类药物的研究主要集中于血管内皮生长因子(VEGF)、人类表皮生长因子受体(HER)家族和磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/m TOR)等信号通路,以及基质金属蛋白酶和环氧化酶-2抑制剂等传统药物。在众多抗血管生成类药物中,胰腺癌治疗领域完成Ⅲ期临床试验并取得成功的仅有厄洛替尼。因此,未来研究的重点应该是探索新靶点的药物,或将多种抗血管生成类药物联合,或将抗血管生成类药物和传统细胞毒药物、其他靶向药物甚至免疫调节药物合理有序的联合用于胰腺癌的治疗中。本文收集国内外近期相关研究和临床试验报道,对胰腺癌抗血管生成治疗的现状和进展作简要综述。

With the deeper research and development of anti-angiogenesis drugs,anti-angiogenesis therapy has become a hot spot in the field of pancreatic cancer. The exploration of anti-angiogenesis therapy for pancreatic cancer is mainly concentrated on drugs that target the vascular endothelial growth factor（ VEGF）,human epidermal growth factor receptor（ HER） family,the phosphatidylinositol-3-kinase/protein kinase/mammalian target of rapamycin（ PI3 K/Akt/m TOR） signaling pathway,as well as some traditional drugs,including matrix metalloproteinase inhibitors and cyclooxygenase-2 inhibitors. In the treatment of pancreatic cancer,the agents which target VEGF signaling pathway include the anti-VEGF monoclonal antibody,the anti-VEGFR drugs（ sorafenib,sunitinib,axitinib and vandetanib）,and the soluble recombinant fusion protein（ aflibercept）. The representative targeted drugs relevant to HER family are cetuximab and erlotinib. Everolimus aimed at PI3 K/Akt/m TOR signaling pathway also have shown great prospect in the phase Ⅱ clinical trials. Currently,just only erlotinib has been completed the phase 3 clinical trials and succeeded. In future,researches should focus on multi-target agents or applications in combination two or three anti-angiogenesis drugs,traditional cytotoxic drugs and even immunomodulatory drugs in the treatment of pancreatic cancer. This review is performed by collecting the recent researches and clinical trials to summarize the current state and progress of research on anti-angiogenesis therapy in pancreatic cancer.