Pancreatic cancer

Definition:

Infiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA). Normal duct epithelium progresses to infiltrating cancer through a series of histologically defined precursors (PanINs). The overexpression of HER-2/neu and activating point mutations in the K-ras gene occur early, inactivation of the p16 gene at an intermediate stage, and the inactivation of p53, SMAD4, and BRCA2 occur relatively late. Activated K-ras engages multiple effector pathways. Although EGF receptors are conventionally regarded as upstream activators of RAS proteins, they can also act as RAS signal transducers via RAS-induced autocrine activation of the EGFR family ligands. Moreover, PDA shows extensive genomic instability and aneuploidy. Telomere attrition and mutations in p53 and BRCA2 are likely to contribute to these phenotypes. Inactivation of the SMAD4 tumour suppressor gene leads to loss of the inhibitory influence of the transforming growth factor-beta signalling pathway.

References:

[1]. Aram F Hezel, et al. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 2006 May 15;20(10):1218-49. [Content Brief]

[2]. Kay L Pogue-Geile, et al. Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PLoS Med. 2006 Dec;3(12):e516. [Content Brief]

[3]. N Bardeesy, et al. The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model. Semin Cancer Biol. 2001 Jun;11(3):201-18. [Content Brief]

[4]. Nabeel Bardeesy, et al. Pancreatic cancer biology and genetics. Nat Rev Cancer. 2002 Dec;2(12):897-909. [Content Brief]

[5]. Sahar Nissim, et al. Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer. Nat Genet. 2019 Sep;51(9):1308-1314. [Content Brief]

[6]. Siân Jones, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009 Apr 10;324(5924):217. [Content Brief]

[7]. Wigdan Al-Sukhni, et al. Germline BRCA1 mutations predispose to pancreatic adenocarcinoma. Hum Genet. 2008 Oct;124(3):271-8. [Content Brief]

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