KEGG   DISEASE: Pancreatic cancerHelp
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
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 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
     Malignant neoplasms of intestine
      Malignant neoplasms of large intestine
       2C10  Malignant neoplasm of pancreas
        H00019  Pancreatic cancer
Tumor markers [br08442.html]
 H00019
Cancer-accociated carbohydrates [br08441.html]
 H00019
BRITE hierarchy
Pathway
hsa05212  Pancreatic cancer
Network
N00012  Mutation-activated KRAS/NRAS to ERK signaling pathway
N00032  Mutation-activated KRAS/NRAS to PI3K signaling pathway
N00034  ERBB2-overexpression to PI3K signaling pathway
N00070  Mutation-inactivated p16(INK4a) to p16-cell cycle G1/S
N00071  Deleted p16(INK4a) to p16-cell cycle G1/S
N00095  ERBB2-overexpression to EGF-Jak-STAT signaling pathway
N00104  Mutation-activated KRAS to RalGDS signaling pathway
N00115  Mutation-inactivated TP53 to transcription
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
Drug
Gemcitabine hydrochloride [DR:D01155]
Paclitaxel [DR:D00491]
Mitomycin [DR:D00208]
Erlotinib hydrochloride [DR:D04023]
Irinotecan hydrochloride [DR:D01061]
Floxuridine [DR:D04197]
Comment
ICD-O: 8500/3, Tumor type: Ductal adenocarcinoma
Other DBs
ICD-11: 2C10.0
ICD-10: C25
MeSH: D010190
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)
DOI:10.1038/nrc949
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)
DOI:10.1101/gad.1415606
Reference
  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
  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)
DOI:10.1016/j.semcancer.2004.06.010
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)
DOI:10.1016/j.lungcan.2004.07.998

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