Department of Medicine, Indiana University School of Medicine, Indianapolis, 46202, United States.
Cancer Treat Rev. 2012 Jun;38(4):272-83. doi: 10.1016/j.ctrv.2011.06.004. Epub 2011 Jul 18.
Results of standard chemotherapy in ovarian cancer are hampered by the development of drug resistance leading to disease recurrence. This prompted interest in the development of therapies targeting critical pathways responsible for tumor progression. Angiogenesis is a key process that enables ovarian cancer growth and metastasis in the peritoneal space. Its regulation relies on signaling mechanisms initiated by the vascular endothelial growth factor, the platelet-derived growth factor, the fibroblast growth factor, angiopoietins, and others. These pathways are not only important to the modulation of the tumor microenvironment and vasculature, but also control cancer cell proliferation and survival. In this review, we discuss preclinical evidence supporting the rationale for inhibiting these pathways and provide an overview for the clinical development of agents targeting them. Clinical trials evaluating such agents alone and in combination with chemotherapy are ongoing. Early clinical results position antiangiogenic therapy at the forefront of change to the standard treatment of difficult to treat ovarian cancer.
标准化疗在卵巢癌中的疗效受到耐药性发展的阻碍,导致疾病复发。这促使人们关注开发针对肿瘤进展关键途径的治疗方法。血管生成是促进卵巢癌细胞在腹膜腔内生长和转移的关键过程。其调节依赖于血管内皮生长因子、血小板衍生生长因子、成纤维细胞生长因子、血管生成素等启动的信号机制。这些途径不仅对肿瘤微环境和血管的调节很重要,而且还控制着癌细胞的增殖和存活。在这篇综述中,我们讨论了支持抑制这些途径的理论基础的临床前证据,并概述了针对这些途径的药物的临床开发。正在进行评估这些药物单独使用和与化疗联合使用的临床试验。早期的临床结果使抗血管生成治疗处于改变难以治疗的卵巢癌标准治疗的前沿。