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Killer on the road?—cells from pancreatic preneoplastic lesions disseminate through pancreatic ducts on their way to cancer

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 392-394页

作者： Heiner Schafer Arne Traulsen susanne sebens Institute for Experimental Cancer Research Kiel University&University Hospital Schleswig-Holstein Campus KielKielGermany Max Planck Institute for Evolutionary Biology PlonGermany

Pancreatic ductal adenocarcinoma (PDAC) is ranked the fourth most common cause of cancer related deaths in western countries with a 5-year survival rate of less than 8% (1). It is estimated to be even the second most common cause by 2030 as there are no successful treatment options (2). Due to the lack of early and specific symptoms as well as non-invasive biomarkers, the majority of patients is diagnosed at an advanced and already metastasized disease stage, where palliative treatment remains the only option (3). Thus, in order to improve the dismal prognosis of PDAC patients, a much better understanding of PDAC evolution is urgently needed allowing earlier detection of the disease and providing novel therapeutic modalities. It is well appreciated that the most common precursor lesion of PDAC is the pancreatic intraepithelial neoplasia (PanIN) (4). According to the progression model (5,6) and supported by genetic studies, PanINs develop from low-grade to high-grade lesions finally leading to an invasive carcinoma. This progression is characterized and driven by the acquisition of genetic (and epigenetic) alterations. In fact, mutations in the oncogene kras, being one of the earliest genetic alterations, are present in 99% of even early low-grade PanINs (PanIN1) (5,6). In resected PDAC tissues, PanINs are often found in and around the tumor mass (7). Genetic analysis revealed that PanINs and adjacent carcinoma tissues share many common mutations albeit some mutations are apparently acquired not until the carcinoma stage (8,9). These data indicate that PDAC may;origin from neighboring PanINs. However, the biology and genetic relationship between PanINs and PDAC and thereby PDAC evolution is still poorly understood.

关键词： alterations Killer thereby

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