The role of stroma in pancreatic cancer: diagnostic and therapeutic implications

被引：513
作者：
Erkan, Mert [1 ]
Hausmann, Simone [1 ]
Michalski, Christoph W. [1 ]
Fingerle, Alexander A. [2 ]
Dobritz, Martin [2 ]
Kleeff, Joerg [1 ]
Friess, Helmut [1 ]
机构：
[1] Tech Univ Munich, Klinikum Rechts Isar, Dept Gen Surg, D-81675 Munich, Germany
[2] Tech Univ Munich, Klinikum Rechts Isar, Inst Radiol, D-81675 Munich, Germany
来源：
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY | 2012年 / 9卷 / 08期
关键词：
FIBROBLAST ACTIVATION PROTEIN; PAPILLARY MUCINOUS NEOPLASMS; RENIN-ANGIOTENSIN SYSTEM; PHASE-III TRIAL; STELLATE CELLS; ELLAGIC ACID; MATRIX METALLOPROTEINASES; TUMOR MICROENVIRONMENT; DUCTAL ADENOCARCINOMA; RECEPTOR ANTAGONISTS;
D O I：
10.1038/nrgastro.2012.115
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Pancreatic ductal adenocarcinoma (PDAC) is one of the five most lethal malignancies worldwide and survival has not improved substantially in the past 30 years. Desmoplasia (abundant fibrotic stroma) is a typical feature of PDAC in humans, and stromal activation commonly starts around precancerous lesions. It is becoming clear that this stromal tissue is not a bystander in disease progression. Cancer-stroma interactions effect tumorigenesis, angiogenesis, therapy resistance and possibly the metastatic spread of tumour cells. Therefore, targeting the tumour stroma, in combination with chemotherapy, is a promising new option for the treatment of PDAC. In this Review, we focus on four issues. First, how can stromal activity be used to detect early steps of pancreatic carcinogenesis? Second, what is the effect of perpetual pancreatic stellate cell activity on angiogenesis and tissue perfusion? Third, what are the (experimental) antifibrotic therapy options in PDAC? Fourth, what lessons can be learned from Langton's Ant (a simple mathematical model) regarding the unpredictability of genetically engineered mouse models?
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页码：454 / 467
页数：14
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