Smolle Elisabeth, Taucher Valentin, Pichler Martin, Petru Edgar, Lax Sigurd, Haybaeck Johannes
Institute of Pathology, Medical University Graz, Auenbruggerplatz 25, A-8036 Graz, Austria.
Int J Mol Sci. 2013 May 2;14(5):9536-55. doi: 10.3390/ijms14059536.
Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies.
We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR) inhibitors, poly-ADP-ribose polymerase (PARP) inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy.
Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.
卵巢癌（OC）是最致命的妇科恶性肿瘤。一些患者对铂类化疗的反应较差，因此，目前的研究集中在新的治疗方案上。OC的各种组织学类型具有与卵巢肿瘤发生相关的独特分子遗传学改变。了解这些分子途径对于开发新的治疗策略至关重要。
我们想概述OC组织病理学类型的分子遗传学变化及其作为潜在治疗靶点的作用。对现有数据的深入综述：2012年，血管内皮生长因子（VEGF）抑制剂贝伐单抗被批准用于OC治疗。贝伐单抗作为单一药物以及与传统化疗联合使用均显示出有前景的结果，但在治疗前分析时其靶点并不独特。目前，雷帕霉素哺乳动物靶点（mTOR）抑制剂、聚ADP核糖聚合酶（PARP）抑制剂和表皮生长因子受体（EGFR）途径的成分是临床研究的重点。有趣的是，一些植物化学物质与化疗联合使用时显示出良好的协同作用。
正在进行的靶向药物与化疗联合的研究将表明，对于OC患者是否有贝伐单抗以外的替代选择。需要在治疗前能够评估以预测疗效的新靶点。通过对肿瘤组织的分子病理学分析，治疗靶点的评估在不断改进。仔细选择患者进行个性化治疗将有助于减少潜在的副作用和毒性。
