Mouse Models in Prostate Cancer Translational Research: From Xenograft to PDX.
Mouse Models in Prostate Cancer Translational Research: From Xenograft to PDX.
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DOI：
10.1155/2016/9750795
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发表时间：
2016
影响因子：
--
通讯作者：
Arra C
中科院分区：
文献类型：
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作者：
Rea D;Del Vecchio V;Palma G;Barbieri A;Falco M;Luciano A;De Biase D;Perdonà S;Facchini G;Arra C
尽管前列腺癌的临床和临床前研究取得了进展，在过去五年中，前列腺癌的发病率下降了3- 4%，但它仍然是男性最常见的癌症，死亡率居第二位。基于这一证据，我们对许多临床前模型进行了简要的论述，比较了它们的优缺点;其中，我们报告了PDX小鼠模型，这些模型在植入肿瘤的组织病理学特征、基因和miRNA表达以及转移模式方面对疾病表现出更高的保真度，很好地描述了所有肿瘤进展阶段;这一特征鼓励了临床前结果的转化。这些模型在根除前列腺癌骨转移瘤生长的新治疗方法鉴定、阐明血管生成途径、鉴定去势抵抗性干细胞样细胞以及研究抗雄激素治疗方面变得特别有用。同样令人感兴趣的是源自PDX的3D细胞培养物的研究，其具有维持PDX细胞活力的能力，同时持续天然雄激素受体表达，也显示出对药物的不同敏感性。3D PDX PCa可能代表快速评估药物的诊断平台，并推动个性化医疗。今天，为了在药物发现的第三阶段之前获得越来越可靠的答案，体外和体内临床前模型的开发是必要的。
Despite the advancement of clinical and preclinical research on PCa, which resulted in the last five years in a decrement of disease incidence by 3-4%, it remains the most frequent cancer in men and the second for mortality rate. Based on this evidence we present a brief dissertation on numerous preclinical models, comparing their advantages and disadvantages; among this we report the PDX mouse models that show greater fidelity to the disease, in terms of histopathologic features of implanted tumor, gene and miRNA expression, and metastatic pattern, well describing all tumor progression stages; this characteristic encourages the translation of preclinical results. These models become particularly useful in meeting the need of new treatments identification that eradicate PCa bone metastases growing, clarifying pathway of angiogenesis, identifying castration-resistant stem-like cells, and studying the antiandrogen therapies. Also of considerable interest are the studies of 3D cell cultures derived from PDX, which have the ability to maintain PDX cell viability with continued native androgen receptor expression, also showing a differential sensitivity to drugs. 3D PDX PCa may represent a diagnostic platform for the rapid assessment of drugs and push personalized medicine. Today the development of preclinical models in vitro and in vivo is necessary in order to obtain increasingly reliable answers before reaching phase III of the drug discovery.