Ovarian Cancer Action Research Centre, Imperial College London Hammersmith Campus, London, UK.
Curr Opin Oncol. 2009 Sep;21(5):412-9. doi: 10.1097/CCO.0b013e32832eab1f.
Clinically and on a molecular level, ovarian cancer is a unique and complex disease. The explosion in potential molecular targets over the last decade has led to the arrival of many novel therapies into oncology. In the present article, we review the most promising of these agents in ovarian cancer.
Targeted therapies, such as epidermal growth factor receptor inhibitors, that have worked well in other cancers have shown only moderate success in ovarian cancer, whereas other treatment approaches have yielded surprisingly positive outcomes. An example is anti-vascular endothelial growth factor and proapoptotic strategies, which are effective in both primary and relapsed ovarian cancer. Use of poly (ADP-ribose)-polymerase inhibitors has shown that targeting one form of DNA repair profoundly affects cell survival in those with a hereditary failure to mend DNA damage using another mechanism. This can be extrapolated to patients with sporadic ovarian cancers, with or without the 'BRCAness' phenotype.
Using targeted agents in ovarian cancer, we are discovering not only how these novel therapies work but are also unveiling the complex 'wiring' of the disease itself, and the interconnections between what were previously believed to be distinct molecular pathways. The addition of targeted agents to our therapeutic armoury is likely to significantly and positively impact on patient survival.
从临床和分子水平来看,卵巢癌是一种独特且复杂的疾病。在过去十年中,潜在的分子靶点大量涌现,许多新的治疗方法也随之进入肿瘤学领域。在本文中,我们综述了卵巢癌中最有前途的这些药物。
在其他癌症中表现良好的靶向治疗药物,如表皮生长因子受体抑制剂,在卵巢癌中的疗效仅为中度,而其他治疗方法则取得了出人意料的积极结果。例如,抗血管内皮生长因子和促凋亡策略在原发性和复发性卵巢癌中均有效。聚(ADP-核糖)聚合酶抑制剂的使用表明,靶向一种 DNA 修复形式会深刻影响那些使用另一种机制修复 DNA 损伤的遗传性缺陷细胞的存活。这可以推断到具有散发性卵巢癌的患者,无论是否具有“BRCA 样”表型。
在卵巢癌中使用靶向药物,我们不仅发现了这些新型疗法的作用机制,还揭示了疾病本身的复杂“连接”,以及以前认为是不同分子途径之间的相互联系。靶向药物的加入可能会对患者的生存产生重大而积极的影响。