Oncology Department, Therapeutics Clinic, Medical School, University of Athens, Athens, Greece.
Onco Targets Ther. 2014 Oct 4;7:1837-45. doi: 10.2147/OTT.S65522. eCollection 2014.
Angiogenesis has been implicated in ovarian cancer pathogenesis. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been incorporated in ovarian cancer treatment in combination with chemotherapy both in a frontline setting and in disease recurrence. However, resistance eventually develops and treatment with bevacizumab is associated with increased risk for toxicities such as thromboembolic and hemorrhagic events, gastrointestinal perforation, and impaired wound healing, suggesting the need for new therapeutic approaches. Targeting of the angiopoietins/Tie2 pathway has gained accumulating interest during the last few years as a strategy to overcome bevacizumab resistance and toxicities. Trebananib is a first-in-class peptibody that inhibits angiopoietin 1 and 2 interaction with their receptor Tie2. The molecular profile of this agent, the preclinical data, and clinical studies demonstrating its efficacy in ovarian cancer are discussed in this review.
血管生成在卵巢癌发病机制中起作用。贝伐珠单抗是一种抗血管内皮生长因子的单克隆抗体，最近已被纳入卵巢癌的治疗方案中，与化疗联合使用，无论是在一线治疗还是疾病复发时。然而，最终会产生耐药性，并且使用贝伐珠单抗与血栓栓塞和出血事件、胃肠道穿孔和伤口愈合受损等毒性增加相关，这表明需要新的治疗方法。在过去几年中，针对血管生成素/Tie2 通路的靶向治疗作为一种克服贝伐珠单抗耐药性和毒性的策略引起了越来越多的关注。Trebananib 是一种首创的肽结合物，可抑制血管生成素 1 和 2 与其受体 Tie2 的相互作用。本文讨论了该药物的分子特征、临床前数据和临床研究，这些研究表明其在卵巢癌中的疗效。
