Aprile Giuseppe, Ongaro Elena, Del Re Marzia, Lutrino Stefania Eufemia, Bonotto Marta, Ferrari Laura, Rihawi Karim, Cardellino Giovanni Gerardo, Pella Nicoletta, Danesi Romano, Fasola Gianpiero
Department of Medical Oncology, University and General Hospital, Udine, Italy.
Department of Medical Oncology, University and General Hospital, Udine, Italy.
Crit Rev Oncol Hematol. 2015 Aug;95(2):165-78. doi: 10.1016/j.critrevonc.2015.02.009. Epub 2015 Mar 5.
Advanced gastric cancer ranks second as the global leading cause of cancer-related death and improvements in systemic chemotherapy have reached a plateau. Advanced molecular sequencing techniques help identifying patients more likely to respond to targeted agents; nevertheless we are still far from major breakthroughs. Although antiangiogenic drugs have produced notable advances, redundant pathways or mechanisms of resistance may limit their efficacy. Novel compounds have been recently developed to specifically target VEGF receptors, PlGF, FGF, MET, and angiopoietin. Ramucirumab, a monoclonal antibody specifically directed against the VEGFR-2, has emerged as a novel therapeutic opportunity. REGARD and RAINBOW were the first phase III studies to report the value of this strategy in gastric cancer patients, and other ongoing trials are testing novel antiangiogenic compounds. The aim of our review is to present the state-of-the-art of novel antiangiogenic compounds in advanced gastric cancer, underlying the biology, their mechanism of action, and their clinical results.
晚期胃癌是全球癌症相关死亡的第二大主要原因，全身化疗的进展已趋于平稳。先进的分子测序技术有助于识别更可能对靶向药物产生反应的患者；然而，我们距离重大突破仍很遥远。尽管抗血管生成药物已取得显著进展，但冗余途径或耐药机制可能会限制其疗效。最近已开发出新型化合物，专门靶向血管内皮生长因子（VEGF）受体、胎盘生长因子（PlGF）、成纤维细胞生长因子（FGF）、间质上皮转化因子（MET）和血管生成素。雷莫西尤单抗是一种特异性针对血管内皮生长因子受体-2（VEGFR-2）的单克隆抗体，已成为一种新的治疗选择。REGARD和RAINBOW是首批报告该策略对胃癌患者价值的III期研究，其他正在进行的试验正在测试新型抗血管生成化合物。我们综述的目的是介绍晚期胃癌新型抗血管生成化合物的最新进展，强调其生物学特性、作用机制和临床结果。
