The promise and challenge of ovarian cancer models.
The promise and challenge of ovarian cancer models.
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DOI：
10.3978/j.issn.2218-676x.2015.01.02
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发表时间：
2015-02
影响因子：
0.9
通讯作者：
Dinulescu DM
中科院分区：
文献类型：
--
作者：
Hasan N;Ohman AW;Dinulescu DM
卵巢癌病例的复杂性和异质性很难在体外研究中重现，这不能充分阐明肿瘤发生和疾病转移所涉及的分子事件。现在已经清楚的是，尽管卵巢癌的多种组织学亚型正在用类似的手术和治疗方法进行治疗，但它们实际上具有不同的表型，细胞起源以及潜在的关键遗传和基因组改变。因此，更个性化的治疗方法的发展，旨在改善患者的护理和预后，将大大受益于更好地了解不同亚型之间的关键差异。为了实现这一目标，需要生成所有组织型的动物模型，以便为靶向治疗和免疫疗法的研究和测试提供准确的体内平台。基因工程小鼠模型（GEMM）和异种移植模型都有能力进一步了解促进肿瘤发生的关键机制，同时提供对增强成像和治疗方式的见解。虽然遗传模型可能更适合于检查肿瘤发生过程中的致癌功能和相互作用，但患者来源的异种移植物（PDX）可能是评估药物疗效的上级模型，特别是在同期临床试验中，因为它们与其来源的肿瘤相似。基因和化身模型具有很大的临床实用性，既有好处，也有局限性。此外，蛋鸡模型，自发发展卵巢肿瘤，具有固有的优势，上皮性卵巢癌（EOC）的研究和最近的工作冠军这个模型，特别是在评估化学预防策略。虽然高级别卵巢浆液性肿瘤是EOC最常见的形式，但罕见的卵巢癌变体，如高钙型小细胞卵巢癌和移行细胞癌，或非上皮性肿瘤，包括生殖细胞肿瘤，也将受益于改进模型的产生，以促进我们对肿瘤发生机制的理解和选择性治疗方案的开发。
The complexity and heterogeneity of ovarian cancer cases are difficult to reproduce in in vitro studies, which cannot adequately elucidate the molecular events involved in tumor initiation and disease metastasis. It has now become clear that, although the multiple histological subtypes of ovarian cancer are being treated with similar surgical and therapeutic approaches, they are in fact characterized by distinct phenotypes, cell of origin, and underlying key genetic and genomic alterations. Consequently, the development of more personalized treatment methodologies, which are aimed at improving patient care and prognosis, will greatly benefit from a better understanding of the key differences between various subtypes. To accomplish this, animal models of all histotypes need to be generated in order to provide accurate in vivo platforms for research and the testing of targeted treatments and immune therapies. Both genetically engineered mouse models (GEMMs) and xenograft models have the ability to further our understanding of key mechanisms facilitating tumorigenesis, and at the same time offer insight into enhanced imaging and treatment modalities. While genetic models may be better suited to examine oncogenic functions and interactions during tumorigenesis, patient-derived xenografts (PDXs) are likely a superior model to assess drug efficacy, especially in concurrent clinical trials, due to their similarity to the tumors from which they are derived. Genetic and avatar models possess great clinical utility and have both benefits and limitations. Additionally, the laying hen model, which spontaneously develops ovarian tumors, has inherent advantages for the study of epithelial ovarian cancer (EOC) and recent work champions this model especially when assessing chemoprevention strategies. While high-grade ovarian serous tumors are the most prevalent form of EOC, rarer ovarian cancer variants, such as small cell ovarian carcinoma of the hypercalcemic type and transitional cell carcinoma, or non-epithelial tumors, including germ cell tumors, will also benefit from the generation of improved models to advance our understanding of tumorigenic mechanisms and the development of selective therapeutic options.