Pathogenesis of pancreatic cancer: lessons from animal models.
Pathogenesis of pancreatic cancer: lessons from animal models.
复制标题
DOI：
10.1177/0192623313508250
复制
发表时间：
2014-01
影响因子：
1.5
通讯作者：
Murtaugh LC
中科院分区：
文献类型：
--
作者：
Murtaugh LC
在过去的几十年里，人们付出了巨大的努力在动物身上模拟胰腺导管腺癌（PDAC）的关键特征，并建立了两种这种致命癌症的可靠模型。用致癌物处理的叙利亚仓鼠会患上具有与人类相似基因损伤的PDAC，包括Kras癌基因的激活，并且在该物种中的早期研究验证了PDAC的非遗传风险因素，如胰腺炎、肥胖和糖尿病。最近，基于组织特异性Kras激活和肿瘤抑制基因缺失的基因工程小鼠模型的发展为PDAC研究注入了活力。令人惊讶的是，小鼠的PDAC似乎是由外分泌腺泡细胞而非导管细胞产生的，是通过一个炎症加速的表型重编程过程。在这两种模型中的研究都揭示了炎症促进和维持PDAC的分子机制，并确定了在高危个体中进行化学预防以抑制PDAC的靶点。特别是小鼠模型，在开发早期检测以及晚期疾病治疗的新方法方面也起到了重要作用。总之，动物模型为胰腺癌的基础和临床前研究提供了多种方法，其研究结果将加速攻克这种目前难以治疗的癌症的进程。
The past several decades have seen great effort devoted to mimicking the key features of pancreatic ductal adenocarcinoma (PDAC) in animals, and have produced two robust models of this deadly cancer. Carcinogen-treated Syrian hamsters develop PDAC with genetic lesions that reproduce those of human, including activation of the Kras oncogene, and early studies in this species validated non-genetic risk factors for PDAC including pancreatitis, obesity and diabetes. More recently, PDAC research has been invigorated by the development of genetically-engineered mouse models based on tissue-specific Kras activation and deletion of tumor suppressor genes. Surprisingly, mouse PDAC appears to arise from exocrine acinar rather than ductal cells, via a process of phenotypic reprogramming that is accelerated by inflammation. Studies in both models have uncovered molecular mechanisms by which inflammation promotes and sustains PDAC, and identified targets for chemoprevention to suppress PDAC in high-risk individuals. The mouse model, in particular, has also been instrumental in developing new approaches to early detection as well as treatment of advanced disease. Together, animal models enable diverse approaches to basic and preclinical research on pancreatic cancer, the results of which will accelerate progress against this currently intractable cancer.
登录
查看更多内容
影响因子：
15.8
作者：
Faca VM;Song KS;Wang H;Zhang Q;Krasnoselsky AL;Newcomb LF;Plentz RR;Gurumurthy S;Redston MS;Pitteri SJ;Pereira-Faca SR;Ireton RC;Katayama H;Glukhova V;Phanstiel D;Brenner DE;Anderson MA;Misek D;Scholler N;Urban ND;Barnett MJ;Edelstein C;Goodman GE;Thornquist MD;McIntosh MW;DePinho RA;Bardeesy N;Hanash SM
通讯作者：
Hanash SM
影响因子：
7.3
作者：
Cleveland, Megan H.;Sawyer, Jacob M.;Afelik, Solomon;Jensen, Jan;Leach, Steven D.
通讯作者：
Leach, Steven D.
影响因子：
15.9
作者：
Collins, Meredith A.;Bednar, Filip;di Magliano, Marina Pasca
通讯作者：
di Magliano, Marina Pasca
影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA
影响因子：
29.4
作者：
Carrière C;Gore AJ;Norris AM;Gunn JR;Young AL;Longnecker DS;Korc M
通讯作者：
Korc M