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前列腺癌转化研究中的小鼠模型:从异种移植到患者来源的肿瘤异种移植模型

Mouse Models in Prostate Cancer Translational Research: From Xenograft to PDX.

作者信息

Rea Domenica, Del Vecchio Vitale, Palma Giuseppe, Barbieri Antonio, Falco Michela, Luciano Antonio, De Biase Davide, Perdonà Sisto, Facchini Gaetano, Arra Claudio

机构信息

Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, 80131 Naples, Italy.

Department of Veterinary Medicine and Animal Productions, Università di Napoli Federico II, Via Delpino 1, 80137 Naples, Italy.

出版信息

Biomed Res Int. 2016;2016:9750795. doi: 10.1155/2016/9750795. Epub 2016 May 18.

Abstract

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.

摘要

尽管前列腺癌的临床和临床前研究取得了进展,使得过去五年疾病发病率下降了3-4%,但它仍是男性中最常见的癌症,死亡率位居第二。基于这一证据,我们对众多临床前模型进行简要论述,比较它们的优缺点;其中我们报告了PDX小鼠模型,该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,能很好地描述所有肿瘤进展阶段;这一特性促进了临床前研究结果的转化。这些模型在满足识别根除生长中的前列腺癌骨转移的新治疗方法、阐明血管生成途径、识别去势抵抗性干细胞样细胞以及研究抗雄激素疗法等需求方面变得尤为有用。源自PDX的3D细胞培养研究也颇受关注,其能够维持PDX细胞活力并持续表达天然雄激素受体,对药物也表现出不同的敏感性。3D PDX前列腺癌模型可能代表了一个用于快速评估药物和推动个性化医疗的诊断平台。如今,为了在药物研发进入III期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。

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