KEGG   DISEASE: Pancreatic cancer
Entry
H00019                      Disease                                
Name
Pancreatic cancer
  Supergrp
Solid tumor [DS:H02421]
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 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
Pathway
hsa05212  Pancreatic cancer
Related
pathway
hsa03440  Homologous recombination
Network
nt06262  Pancreatic cancer
Gene
KRAS [HSA:3845] [KO:K07827]
TP53 [HSA:7157] [KO:K04451]
SMAD4 [HSA:4089] [KO:K04501]
STK11 [HSA:6794] [KO:K07298]
ERBB2 (overexpression) [HSA:2064] [KO:K05083]
CDKN2A (mutation, deletion, promoter methylation) [HSA:1029] [KO:K06621]
(PNCA1) PALLD [HSA:23022] [KO:K22029]
(PNCA2) BRCA2 [HSA:675] [KO:K08775]
(PNCA3) PALB2 [HSA:79728] [KO:K10897]
(PNCA4) BRCA1 [HSA:672] [KO:K10605]
(PNCA5) RABL3 [HSA:285282] [KO:K07933]
Drug
Gemcitabine hydrochloride [DR:D01155]
Floxuridine [DR:D04197]
Paclitaxel [DR:D00491]
Irinotecan hydrochloride [DR:D01061]
Mitomycin [DR:D00208]
Erlotinib hydrochloride [DR:D04023]
Olaparib [DR:D09730] (BRCA-mutated)
Other DBs
ICD-11: 2C10.0
ICD-10: C25
MeSH: D010190
OMIM: 606856 613347 613348 614320 618680
Reference
PMID:12459728 (KRAS, TP53, SMAD4, STK11, ERBB2, CDKN2A, BRCA2)
  Authors
Bardeesy N, DePinho RA.
  Title
Pancreatic cancer biology and genetics.
  Journal
Nat Rev Cancer 2:897-909 (2002)
DOI:10.1038/nrc949
Reference
  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: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.
  Journal
Science 324:217 (2009)
DOI:10.1126/science.1171202
Reference
PMID:18762988 (BRCA1)
  Authors
Al-Sukhni W, Rothenmund H, Borgida AE, Zogopoulos G, O'Shea AM, Pollett A, Gallinger S
  Title
Germline BRCA1 mutations predispose to pancreatic adenocarcinoma.
  Journal
Hum Genet 124:271-8 (2008)
DOI:10.1007/s00439-008-0554-0
Reference
PMID:31406347 (RABL3)
  Authors
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.
  Journal
Nat Genet 51:1308-1314 (2019)
DOI:10.1038/s41588-019-0475-y

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