Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy.
Cancer Treat Rev. 2013 Oct;39(6):561-8. doi: 10.1016/j.ctrv.2013.01.005. Epub 2013 Feb 19.
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite progress in identifying "hallmark" genetic alterations associated with the main subtypes of epithelial ovarian cancer, the survival rate of women with EOC changed little since platinum-based treatment was introduced more than 30years ago. The successful identification of new, effective anticancer drugs largely depends on appropriate preclinical experimental models that should ideally mimic the complexity of different cancer forms. This review examines the preclinical ovarian cancer models available for a better understanding of the biological mechanisms of the development, progression, invasion and metastasis of EOC. We provide evidence that the preclinical models have been instrumental for a better understanding of the pathological events at the basis of ovarian carcinoma. The genetically engineered mouse (GEM) models of ovarian cancer have overcome some of the weaknesses of the xenograft models, such as the fact that these tumors arise orthotopically in immunologically intact mice and more closely resemble the behavior of human cancers. We envisage that in the near future these GEM models will play a key role in pre-selecting drug regimens with the greatest promise of efficacy in human clinical trials, making it easier and certainly less expensive to test new, different drug combinations.
上皮性卵巢癌 (EOC) 是最致命的妇科恶性肿瘤。尽管在确定与上皮性卵巢癌主要亚型相关的“标志性”遗传改变方面取得了进展，但自 30 多年前引入基于铂类的治疗以来，EOC 患者的生存率几乎没有变化。新的有效抗癌药物的成功鉴定在很大程度上取决于适当的临床前实验模型，这些模型应理想地模拟不同癌症形式的复杂性。这篇综述检查了现有的临床前卵巢癌模型，以更好地了解 EOC 的发展、进展、侵袭和转移的生物学机制。我们提供的证据表明，临床前模型对于更好地理解卵巢癌基础上的病理事件是至关重要的。卵巢癌的基因工程小鼠 (GEM) 模型克服了异种移植模型的一些弱点，例如这些肿瘤在免疫完整的小鼠中原位发生，并且更类似于人类癌症的行为。我们预计，在不久的将来，这些 GEM 模型将在预先选择最有希望在人类临床试验中有效治疗方案方面发挥关键作用，从而更容易且肯定更廉价地测试新的、不同的药物组合。
