KEGG   DISEASE: Pancreatic cancer
H00019                      Disease                                
Pancreatic cancer
Solid tumor [DS:H02421]
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. 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.
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
Pathway-based classification of diseases [BR:br08402]
 Replication and repair
  nt06506  Double-strand break repair
   H00019  Pancreatic cancer
  nt06508  Interstrand crosslink repair
   H00019  Pancreatic cancer
 Signal transduction
  nt06526  MAPK signaling
   H00019  Pancreatic cancer
Tumor markers [br08442.html]
Cancer-associated carbohydrates [br08441.html]
hsa05212  Pancreatic cancer
nt06262 Pancreatic cancer
nt06506 Double-strand break repair
nt06508 Interstrand crosslink repair
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]
Gemcitabine hydrochloride [DR:D01155]
Capecitabine [DR:D01223]
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
PMID:12459728 (KRAS, TP53, SMAD4, STK11, ERBB2, CDKN2A, BRCA2)
Bardeesy N, DePinho RA.
Pancreatic cancer biology and genetics.
Nat Rev Cancer 2:897-909 (2002)
Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA.
Genetics and biology of pancreatic ductal adenocarcinoma.
Genes Dev 20:1218-49 (2006)
Bardeesy N, Sharpless NE, DePinho RA, Merlino G.
The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model.
Semin Cancer Biol 11:201-18 (2001)
Hruban RH, Goggins M, Parsons J, Kern SE.
Progression model for pancreatic cancer.
Clin Cancer Res 6:2969-72 (2000)
PMID:17194196 (PALLD)
Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, Dowen S, Otey CA, Crispin DA, George RD, Whitcomb DC, Brentnall TA
Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism.
PLoS Med 3:e516 (2006)
PMID:19264984 (PALB2)
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
Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.
Science 324:217 (2009)
PMID:18762988 (BRCA1)
Al-Sukhni W, Rothenmund H, Borgida AE, Zogopoulos G, O'Shea AM, Pollett A, Gallinger S
Germline BRCA1 mutations predispose to pancreatic adenocarcinoma.
Hum Genet 124:271-8 (2008)
PMID:31406347 (RABL3)
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
Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer.
Nat Genet 51:1308-1314 (2019)

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