| H00019 | |
| H number | H00019 |
| 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. 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 DIS_PATHWAY hsa05212 Pancreatic cancer |
| 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] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | 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) |
| Comment | - |
| 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 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 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 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) 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 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 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 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 |