文章：

化疗之外：卵巢癌的靶向治疗

Beyond chemotherapy: targeted therapies in ovarian cancer

原文发布日期：2009-02-01

DOI: 10.1038/nrc2583

类型: Review Article

开放获取: 否

要点：

1. Although the results of treatment with conventional chemotherapy and surgery for advanced ovarian cancer have gradually improved, the majority of women still die with drug-resistant disease after 5 years. Our improved understanding of the underlying biology of ovarian cancer is now leading to the development of molecular targeted therapies, which aim to address this major clinical need.
2. Anti-angiogenic cancer therapies such as bevacizumab have shown efficacy in early-phase ovarian cancer clinical trials and are likely to become part of standard therapy for advanced ovarian cancer in the future.
3. A poly (ADP-ribose) polymerase inhibitor has shown substantial anti-tumour activity as a single-agent therapy in germline BRCA-deficient patients with ovarian cancer in early clinical trials; further studies assessing its role in sporadic ovarian cancers are now underway.
4. Genetic and epigenetic aberrations that drive ovarian cancer have been discovered. These drive key oncogenic signalling pathways, such as the PI3K–Akt pathway, and might be potential targets for anticancer therapeutics, either as monotherapy or in combination with established cytotoxic chemotherapies.
5. Pharmacodynamic biomarkers, which provide proof-of-principle of target modulation and predictive biomarkers, which could be used for patient selection, are essential in the development of novel molecular targeted therapies for ovarian cancer.
6. It is expected that the development of novel anticancer therapies, particularly as maintenance treatments, might lead to the prolonged survival of patients with ovarian tumours in the future.

要点翻译：

1. 尽管晚期卵巢癌的常规化疗和手术治疗效果已逐步提高，但大多数患者仍在5年内死于耐药性疾病。如今，我们对卵巢癌潜在生物学机制的深入认识正推动分子靶向疗法的研发，旨在解决这一重大临床需求。
2. 抗血管生成癌症疗法（如贝伐单抗）在早期卵巢癌临床试验中已显示疗效，未来有望成为晚期卵巢癌标准治疗方案的一部分。
3. 在早期临床试验中，聚腺苷二磷酸核糖聚合酶抑制剂作为单药疗法在种系BRCA缺陷的卵巢癌患者中显示出显著抗肿瘤活性；目前正在开展进一步研究评估其在散发性卵巢癌中的作用。
4. 已发现驱动卵巢癌发生的遗传学与表观遗传学异常。这些异常会激活关键致癌信号通路（如PI3K-Akt通路），可能成为抗癌治疗的潜在靶点，既可单独应用也可与现有细胞毒性化疗联合使用。
5. 药效学生物标志物可提供靶点调控的原理验证，预测性生物标志物可用于患者筛选，这两者在开发卵巢癌新型分子靶向疗法中具有关键作用。
6. 预计新型抗癌疗法的开发，特别是作为维持治疗手段，未来可能延长卵巢癌患者的生存期。

英文摘要：

Ovarian cancer is the leading cause of death from gynaecological malignancies in the Western world. Despite the evolution of surgical techniques and meticulously designed chemotherapy regimens, relapse remains almost inevitable in patients with advanced disease. In an age when great advances have been made in understanding the genetics and molecular biology of this heterogeneous disease, it is likely that the introduction of novel targeted therapies will have a major impact on the management of ovarian cancer. Importantly, such strategies might allow selection of treatments based on the molecular characteristics of tumours and bring us closer to an era of personalized medicine.

摘要翻译： 

卵巢癌是西方世界妇科恶性肿瘤死亡的主要原因。尽管手术技术不断演进，化疗方案精心设计，晚期患者复发仍几乎不可避免。在当下，我们对这种异质性疾病的遗传学和分子生物学认识已突飞猛进，引入新型靶向治疗有望极大改变卵巢癌的管理模式。关键在于，这些策略可依据肿瘤的分子特征选择治疗，使我们更接近个体化医疗时代。

原文链接：

Beyond chemotherapy: targeted therapies in ovarian cancer