Al Wadi Khalid, Ghatage Prafull
a Division of Gynecologic Oncology , Tom Baker Cancer Centre , Calgary , AB , Canada.
b Women's Specialized Hospital, King Fahad Medical City , Riyadh , Saudi Arabia.
Expert Opin Pharmacother. 2016;17(6):853-60. doi: 10.1517/14656566.2016.1161027. Epub 2016 Mar 21.
Epithelial ovarian cancer (EOC) is the leading cause of death among gynecologic cancers. The majority of women are diagnosed with advanced stage disease. It is considered a chemosensitive cancer with a high initial response rate to first-line platinum and taxane-based chemotherapy. However, most patients with advanced EOC will relapse with subsequent resistance to conventional chemotherapy and ultimately succumb to their disease. Therefore, new therapeutic agents and strategies are desperately needed to improve the outcomes in patients with advanced EOC.
This review focuses on the use of Trebananib (a non-VEGF-dependent angiogenesis pathway inhibitor) in EOC. Angiogenesis has been recognized as an important process promoting EOC growth and metastasis. Targeting angiogenesis in EOC have been developed and studied with demonstrated clinical efficacy. Bevacizumab, a humanized monoclonal antibody, that targets vascular endothelial growth factor A (VEGF-A), has been the most well evaluated molecular targeted therapy in the treatment of advanced and recurrent EOC with proven clinical efficacy. However, VEGF-dependent angiogenesis pathway inhibitors are often associated with serious toxicities and drug resistance ultimately develops. Hence, new therapeutic approach targeting the angiopoietin-Tie-2 complex pathway (a non-VEGF-dependent angiogenesis pathway) has gained interest over the past few years as an alternative strategy to overcome VEGF-dependent anti-angiogenesis-related toxicity and resistance.
Targeting angiopoietin-Tie-2 pathway represents a promising alternative approach to tumor anti-angiogenesis with a distinct toxicity profile from the VEGF-dependent pathway inhibitors. However, there are still many questions to be answered regarding the optimal treatment schedules, maintenance regimens, duration of maintenance therapy, and the best combination strategy. Currently there is no reliable surrogate molecular, cellular, or genetic marker that would definitively predict response to anti-angiogenic therapy. Identification of certain relevant and predictive biomarkers in the future may optimize treatment's efficacy by distinguishing the subset group of patients with EOC that would derive the most benefit from existing antiangiogenic treatment regimens.
上皮性卵巢癌（EOC）是妇科癌症死亡的主要原因。大多数女性被诊断为晚期疾病。它被认为是一种对化疗敏感的癌症，对一线铂类和紫杉烷类化疗的初始反应率很高。然而，大多数晚期EOC患者会复发，并随后对传统化疗产生耐药性，最终死于该疾病。因此，迫切需要新的治疗药物和策略来改善晚期EOC患者的治疗结果。
本综述重点关注曲贝替定（一种非VEGF依赖性血管生成途径抑制剂）在EOC中的应用。血管生成已被认为是促进EOC生长和转移的重要过程。针对EOC中的血管生成已开发并进行了研究，显示出临床疗效。贝伐单抗是一种靶向血管内皮生长因子A（VEGF-A）的人源化单克隆抗体，是治疗晚期和复发性EOC中评估最充分的分子靶向治疗药物，已证实具有临床疗效。然而，VEGF依赖性血管生成途径抑制剂通常与严重毒性相关，最终会产生耐药性。因此，在过去几年中，靶向血管生成素-Tie-2复合物途径（一种非VEGF依赖性血管生成途径）作为克服VEGF依赖性抗血管生成相关毒性和耐药性的替代策略引起了人们的关注。
靶向血管生成素-Tie-2途径代表了一种有前景的肿瘤抗血管生成替代方法，其毒性特征与VEGF依赖性途径抑制剂不同。然而，关于最佳治疗方案、维持治疗方案、维持治疗持续时间以及最佳联合策略仍有许多问题有待解答。目前尚无可靠的替代分子、细胞或遗传标志物能够明确预测对抗血管生成治疗的反应。未来确定某些相关和预测性生物标志物可能通过区分EOC患者亚组来优化治疗效果，这些患者将从现有的抗血管生成治疗方案中获益最大。
