Morin Patrice J, Weeraratna Ashani T
American Association for Cancer Research, Philadelphia, PA 19106, USA.
Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
J Pathol. 2016 Jan;238(2):180-4. doi: 10.1002/path.4663.
Epithelial ovarian cancer (EOC), the deadliest of gynaecological cancers, is a disease that remains difficult to detect early and treat efficiently. A significant challenge for researchers in the field is that the aetiology of EOC and the molecular pathways important for its development are poorly understood. Moreover, precursor lesions have not been readily identifiable, making the mechanisms of EOC progression difficult to delineate. In order to address these issues, several genetically-defined ovarian mouse models have been generated in the past 15 years. However, because of the recent suggestion that most EOCs may not originate from the ovarian surface 'epithelium', but from other tissues of the female genital tract, some models may need to be re-evaluated within this new paradigm. In this review, we examine several genetically-defined EOC models and discuss how the new paradigm may explain some of the features of these models. A better understanding of the strengths and limitations of the current EOC mouse models will undoubtedly allow us to utilize these tools to better understand the biology of the disease and develop new approaches for EOC prevention, detection, and treatment.
上皮性卵巢癌(EOC)是最致命的妇科癌症,是一种仍然难以早期检测和有效治疗的疾病。该领域研究人员面临的一个重大挑战是,对EOC的病因及其发展的重要分子途径了解甚少。此外,尚未能轻易识别前驱病变,这使得EOC进展的机制难以描述。为了解决这些问题,在过去15年中已经建立了几种基因定义的卵巢小鼠模型。然而,由于最近有人提出大多数EOC可能并非起源于卵巢表面“上皮”,而是来自女性生殖道的其他组织,因此在这种新范式下可能需要重新评估一些模型。在本综述中,我们研究了几种基因定义的EOC模型,并讨论新范式如何解释这些模型的一些特征。更好地了解当前EOC小鼠模型的优势和局限性无疑将使我们能够利用这些工具更好地理解该疾病的生物学特性,并开发预防、检测和治疗EOC的新方法。