Secord Angeles Alvarez, Nixon Andrew B, Hurwitz Herbert I
Duke University Medical Center, Durham, NC, USA.
Duke University Medical Center, Durham, NC, USA.
Gynecol Oncol. 2014 Nov;135(2):349-58. doi: 10.1016/j.ygyno.2014.08.033. Epub 2014 Aug 30.
Antiangiogenic agents have demonstrated improved progression-free survival in women with primary and recurrent epithelial ovarian cancer (EOC). Biomarkers that predict outcomes in patients treated with antiangiogenic agents are being investigated to rationally direct therapy for women most likely to benefit from these agents. Among the most promising plasma-based biomarkers are vascular endothelial growth factor (VEGF)-A, fibroblast growth factor, platelet-derived growth factor, angiopoietin-2, and VEGF receptor-2. While these biomarkers have been correlated with prognosis, they have not been shown to predict benefit, specifically from anti-VEGF therapy, highlighting the need for alternative biomarkers, including molecular and clinical factors, which may be predictive of outcome in women with ovarian cancer treated with antiangiogenic agents. Biomarkers are currently being investigated as secondary outcomes in several ongoing phase II and phase III clinical trials of antiangiogenic agents in patients with EOC. Molecular techniques, such as microarray analyses, and imaging techniques, such as dynamic contrast-enhanced magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, are also being explored in this field. In this review, we provide a comprehensive overview of current biomarker research, with an emphasis on angiogenic biomarkers associated with EOC.
抗血管生成药物已显示可改善原发性和复发性上皮性卵巢癌(EOC)女性患者的无进展生存期。目前正在研究预测抗血管生成药物治疗患者预后的生物标志物,以便合理地指导最有可能从这些药物中获益的女性患者的治疗。最有前景的基于血浆的生物标志物包括血管内皮生长因子(VEGF)-A、成纤维细胞生长因子、血小板衍生生长因子、血管生成素-2和VEGF受体-2。虽然这些生物标志物与预后相关,但尚未显示它们能预测获益情况,尤其是抗VEGF治疗的获益情况,这凸显了对包括分子和临床因素在内的替代生物标志物的需求,这些生物标志物可能预测接受抗血管生成药物治疗的卵巢癌女性患者的预后。目前,生物标志物正在EOC患者抗血管生成药物的多项正在进行的II期和III期临床试验中作为次要结局进行研究。分子技术,如微阵列分析,以及成像技术,如动态对比增强磁共振成像、正电子发射断层扫描和单光子发射计算机断层扫描,也正在该领域进行探索。在本综述中,我们全面概述了当前的生物标志物研究,重点是与EOC相关的血管生成生物标志物。