Although the estimated time for development of pancreatic ductal adenocarcinoma (PDA) is more than 20 years, PDAs are usually detected at late, metastatic stages. PDAs develop from duct-like cells through a multistep carcinogenesis process, from low-grade dysplastic lesions to carcinoma in situ and eventually to metastatic disease. This process involves gradual acquisition of mutations in oncogenes and tumor suppressor genes, as well as changes in the pancreatic environment from a pro-inflammatory microenvironment that favors the development of early lesions, to a desmoplastic tumor microenvironment that is highly fibrotic and immune suppressive. This review discusses our current understanding of how PDA originates.
Keywords: Carcinogenesis; Desmoplastic Reaction; Microenvironment; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraepithelial Neoplasia.
Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.
Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma.Mod Pathol. 2003 Oct;16(10):996-1006. doi: 10.1097/01.MP.0000087422.24733.62. Mod Pathol. 2003. PMID: 14559982
hsa-miR-96 and hsa-miR-217 Expression Down-Regulates with Increasing Dysplasia in Pancreatic Intraepithelial Neoplasias and Intraductal Papillary Mucinous Neoplasms.Int J Med Sci. 2017 Apr 8;14(5):412-418. doi: 10.7150/ijms.18641. eCollection 2017. Int J Med Sci. 2017. PMID: 28539816 Free PMC article.
Overexpression of G1-S cyclins and cyclin-dependent kinases during multistage human pancreatic duct cell carcinogenesis.Clin Cancer Res. 2004 Oct 1;10(19):6598-605. doi: 10.1158/1078-0432.CCR-04-0524. Clin Cancer Res. 2004. PMID: 15475449
[Precursors to pancreatic cancer].Tidsskr Nor Laegeforen. 2006 Mar 23;126(7):905-8. Tidsskr Nor Laegeforen. 2006. PMID: 16554881 Review. Norwegian.
Gemcitabine resistance in pancreatic ductal adenocarcinoma.Drug Resist Updat. 2015 Nov;23:55-68. doi: 10.1016/j.drup.2015.10.002. Epub 2015 Nov 3. Drug Resist Updat. 2015. PMID: 26690340 Review.
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Current Strategies and Future Perspectives for Precision Medicine in Pancreatic Cancer.Cancers (Basel). 2020 Apr 21;12(4):1024. doi: 10.3390/cancers12041024. Cancers (Basel). 2020. PMID: 32326341 Free PMC article. Review.