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胰腺癌小鼠模型的当前方法。

Current methods in mouse models of pancreatic cancer.

作者信息

Mazur Pawel K, Herner Alexander, Neff Florian, Siveke Jens T

机构信息

Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA.

出版信息

Methods Mol Biol. 2015;1267:185-215. doi: 10.1007/978-1-4939-2297-0_9.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the Western world. The disease has the worst prognosis in the gastrointestinal malignancies with an overall 5-year survival rate of less than 5 %. Therefore, in the search for novel therapeutic targets, biomarkers for early detection and particularly adequate methods to develop and validate therapeutic strategies for this disease are still in urgent demand. Although significant progress has been achieved in understanding the genetic and molecular mechanisms, most approaches have not yet translated sufficiently for better outcome of the patients. In part, this situation is due to inappropriate or insufficient methods in modeling PDAC in laboratory settings. In the past several years, there has been an explosion of genetically engineered mouse models (GEMM) and patient-derived xenografts (PDX) that recapitulate both genetic and morphological alterations that lead to the development of PDAC. Both models are increasingly used for characterization and validation of diagnostic and therapeutic strategies. In this chapter we will discuss state-of-the-art models to consider when selecting an appropriate in vivo system to study disease etiology, cell signaling, and drug development.

摘要

胰腺导管腺癌(PDAC)是西方世界癌症死亡的第四大主要原因。该疾病在胃肠道恶性肿瘤中预后最差,总体5年生存率不到5%。因此,在寻找新的治疗靶点方面,早期检测的生物标志物,尤其是开发和验证该疾病治疗策略的适当方法,仍然迫切需要。尽管在理解遗传和分子机制方面取得了重大进展,但大多数方法尚未充分转化以改善患者的预后。部分原因是在实验室环境中模拟PDAC的方法不当或不足。在过去几年中,出现了大量的基因工程小鼠模型(GEMM)和患者来源的异种移植模型(PDX),它们再现了导致PDAC发生的遗传和形态学改变。这两种模型越来越多地用于诊断和治疗策略的表征和验证。在本章中,我们将讨论在选择合适的体内系统来研究疾病病因、细胞信号传导和药物开发时需要考虑的最新模型。

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