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.
Category
Cancer
Brite
Human diseases [BR:br08402]
Cancers
Cancers of the digestive system
H00019 Pancreatic cancer
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Malignant neoplasms, except primary neoplasms of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms of digestive organs
2C10 Malignant neoplasm of pancreas
H00019 Pancreatic cancer
Tumor markers [br08442.html]
H00019
Cancer-associated carbohydrates [br08441.html]
H00019
Nat Rev Cancer 2:897-909 (2002) DOI:10.1038/nrc949
Reference
PMID:16702400
Authors
Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA.
Title
Genetics and biology of pancreatic ductal adenocarcinoma.
Journal
Genes Dev 20:1218-49 (2006) DOI:10.1101/gad.1415606
Reference
PMID:11407945
Authors
Bardeesy N, Sharpless NE, DePinho RA, Merlino G.
Title
The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model.
Journal
Semin Cancer Biol 11:201-18 (2001) DOI:10.1006/scbi.2000.0371
Reference
PMID:10955772
Authors
Hruban RH, Goggins M, Parsons J, Kern SE.
Title
Progression model for pancreatic cancer.
Journal
Clin Cancer Res 6:2969-72 (2000)
Reference
PMID:17194196 (PALLD)
Authors
Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, Dowen S, Otey CA, Crispin DA, George RD, Whitcomb DC, Brentnall TA
Title
Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism.
Journal
PLoS Med 3:e516 (2006) DOI:10.1371/journal.pmed.0030516
Reference
PMID:19264984 (PALB2)
Authors
Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP
Title
Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.
Nissim S, Leshchiner I, Mancias JD, Greenblatt MB, Maertens O, Cassa CA, Rosenfeld JA, Cox AG, Hedgepeth J, Wucherpfennig JI, Kim AJ, Henderson JE, Gonyo P, Brandt A, Lorimer E, Unger B, Prokop JW, Heidel JR, Wang XX, Ukaegbu CI, Jennings BC, Paulo JA, Gableske S, Fierke CA, Getz G, Sunyaev SR, Wade Harper J, Cichowski K, Kimmelman AC, Houvras Y, Syngal S, Williams C, Goessling W
Title
Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer.