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Cold Spring Harbor, NY, United States

Hwang C.-I.,Cold Spring Harbor Laboratory | Hwang C.-I.,Lustgarten Foundation Pancreatic Cancer Research Laboratory | Boj S.F.,Netherlands Cancer Institute | Clevers H.,Netherlands Cancer Institute | And 2 more authors.
Journal of Pathology | Year: 2016

Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult human malignancies to treat. The 5-year survival rate of PDA patients is 7% and PDA is predicted to become the second leading cancer-related cause of death in the USA. Despite intensive efforts, the translation of findings in preclinical studies has been ineffective, due partially to the lack of preclinical models that faithfully recapitulate features of human PDA. Here, we review current preclinical models for human PDA (eg human PDA cell lines, cell line-based xenografts and patient-derived tumour xenografts). In addition, we discuss potential applications of the recently developed pancreatic ductal organoids, three-dimensional culture systems and organoid-based xenografts as new preclinical models for PDA. © 2015 Pathological Society of Great Britain and Ireland.

Boj S.F.,University Utrecht | Hwang C.-I.,Cold Spring Harbor Laboratory | Hwang C.-I.,Lustgarten Foundation Pancreatic Cancer Research Laboratory | Baker L.A.,Cold Spring Harbor Laboratory | And 74 more authors.
Cell | Year: 2015

Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. © 2015 Elsevier Inc. All rights reserved.

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