| H00019 | |
| H番号 | H00019 |
| 名称 | 膵癌 |
| 概要 | 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. |
| カテゴリ | がん 疾患パスウェイ hsa05212 膵癌 |
| ネットワーク | nt06262 Pancreatic cancer |
| 病因遺伝子 | 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] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | マイトマイシンC [DR:D00208] レボホリナートカルシウム水和物 [DR:D11555] シクロホスファミド水和物 [DR:D00287] フルオロウラシル [DR:D00584] シタラビン [DR:D00168] ゲムシタビン塩酸塩 [DR:D01155] テガフール・ウラシル [DR:D02131] テガフール・ギメラシル・オテラシルカリウム [DR:D06399] ドキソルビシン塩酸塩 [DR:D01275] パクリタキセル [DR:D00491] イリノテカン塩酸塩水和物 [DR:D01061] エルロチニブ塩酸塩 [DR:D04023] オキサリプラチン [DR:D01790] オラパリブ [DR:D09730] (BRCA遺伝子変異陽性) |
| コメント | - |
| リンク | ICD-11: 2C10.0 ICD-10: C25 MeSH: D010190 OMIM: 606856 613347 613348 614320 618680 |
| 文献 | PMID:12459728 (KRAS, TP53, SMAD4, STK11, ERBB2, CDKN2A, BRCA2) 著者 Bardeesy N, DePinho RA. タイトル Pancreatic cancer biology and genetics. 雑誌 Nat Rev Cancer 2:897-909 (2002) DOI:10.1038/nrc949 PMID:16702400 著者 Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA. タイトル Genetics and biology of pancreatic ductal adenocarcinoma. 雑誌 Genes Dev 20:1218-49 (2006) DOI:10.1101/gad.1415606 PMID:11407945 著者 Bardeesy N, Sharpless NE, DePinho RA, Merlino G. タイトル The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model. 雑誌 Semin Cancer Biol 11:201-18 (2001) DOI:10.1006/scbi.2000.0371 PMID:10955772 著者 Hruban RH, Goggins M, Parsons J, Kern SE. タイトル Progression model for pancreatic cancer. 雑誌 Clin Cancer Res 6:2969-72 (2000) PMID:17194196 (PALLD) 著者 Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, Dowen S, Otey CA, Crispin DA, George RD, Whitcomb DC, Brentnall TA タイトル Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. 雑誌 PLoS Med 3:e516 (2006) DOI:10.1371/journal.pmed.0030516 PMID:19264984 (PALB2) 著者 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 タイトル Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. 雑誌 Science 324:217 (2009) DOI:10.1126/science.1171202 PMID:18762988 (BRCA1) 著者 Al-Sukhni W, Rothenmund H, Borgida AE, Zogopoulos G, O'Shea AM, Pollett A, Gallinger S タイトル Germline BRCA1 mutations predispose to pancreatic adenocarcinoma. 雑誌 Hum Genet 124:271-8 (2008) DOI:10.1007/s00439-008-0554-0 PMID:31406347 (RABL3) 著者 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 タイトル Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer. 雑誌 Nat Genet 51:1308-1314 (2019) DOI:10.1038/s41588-019-0475-y |