KEGG   DISEASE: H00019Help
Entry
H00019                      Disease                                

Name
Pancreatic cancer
Description
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 hierarchy
Pathway
Pancreatic cancer
Gene
K-ras (mutation) [HSA:3845] [KO:K07827]
ERBB2 (overexpression) [HSA:2064] [KO:K05083]
p16/INK4A (mutation, deletion, promoter methylation) [HSA:1029] [KO:K06621]
p53 (mutation) [HSA:7157] [KO:K04451]
SMAD4 (mutation) [HSA:4089] [KO:K04501]
BRCA2 (germline mutation) [HSA:675] [KO:K08775]
STK11 (germline mutation) [HSA:6794] [KO:K07298]
Carcinogen
Tobacco smoking and tobacco smoke
Marker
MIC-1 [HSA:9518]
CA19-9
Osteopontin [HSA:6696]
K-ras (mutation) [HSA:3845]
p53 (mutation) [HSA:7157]
Drug
Fluorouracil [DG:DG00687]
ELF
Gemcitabine [DG:DG00688]
Erlotinib [DG:DG00711]
Comment
ICD-O: 8500/3, Tumor type: Ductal adenocarcinoma
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:12459728 (gene, tumor type)
  Authors
Bardeesy N, DePinho RA.
  Title
Pancreatic cancer biology and genetics.
  Journal
Nat Rev Cancer 2:897-909 (2002)
Reference
PMID:16702400 (tumor type)
  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)
Reference
PMID:11407945 (gene)
  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)
Reference
PMID:10955772 (gene)
  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:15489140 (carcinogen)
  Authors
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.
  Title
Environmental and chemical carcinogenesis.
  Journal
Semin Cancer Biol 14:473-86 (2004)
Reference
PMID:15552776 (carcinogen)
  Authors
Sasco AJ, Secretan MB, Straif K.
  Title
Tobacco smoking and cancer: a brief review of recent epidemiological evidence.
  Journal
Lung Cancer 45 Suppl 2:S3-9 (2004)
Reference
PMID:16648548 (marker)
  Authors
Jimeno A, Hidalgo M.
  Title
Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer.
  Journal
Mol Cancer Ther 5:787-96 (2006)
Reference
PMID:16002843 (marker)
  Authors
Goggins M.
  Title
Molecular markers of early pancreatic cancer.
  Journal
J Clin Oncol 23:4524-31 (2005)
Reference
(drug)
  Authors
McPhee SJ, Papadakis MA, Tierney LM (ed).
  Title
Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition
  Journal
The McGraw-Hill Companies, Inc. (2007)

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