Pancreatic cancer

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.

Cancer

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]

Tobacco smoking and tobacco smoke

MIC-1 [HSA:9518]
CA19-9
Osteopontin [HSA:6696]
K-ras (mutation) [HSA:3845]
p53 (mutation) [HSA:7157]

Fluorouracil [DR:D00584]
ELF
Gemcitabine [DR:D02368 D01155]
Erlotinib [DR:D04023]

ICD-O: 8500/3, Tumor type: Ductal adenocarcinoma

PMID:12459728 (gene, tumor type)

Bardeesy N, DePinho RA.

Pancreatic cancer biology and genetics.

Nat Rev Cancer 2:897-909 (2002)

PMID:16702400 (tumor type)

Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA.

Genetics and biology of pancreatic ductal adenocarcinoma.

Genes Dev 20:1218-49 (2006)

PMID:11407945 (gene)

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)

PMID:10955772 (gene)

Hruban RH, Goggins M, Parsons J, Kern SE.

Progression model for pancreatic cancer.

Clin Cancer Res 6:2969-72 (2000)

PMID:15489140 (carcinogen)

Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.

Environmental and chemical carcinogenesis.

Semin Cancer Biol 14:473-86 (2004)

PMID:15552776 (carcinogen)

Sasco AJ, Secretan MB, Straif K.

Tobacco smoking and cancer: a brief review of recent epidemiological evidence.

Lung Cancer 45 Suppl 2:S3-9 (2004)

PMID:16648548 (marker)

Jimeno A, Hidalgo M.

Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer.

Mol Cancer Ther 5:787-96 (2006)

PMID:16002843 (marker)

Goggins M.

Molecular markers of early pancreatic cancer.

J Clin Oncol 23:4524-31 (2005)

(drug)

McPhee SJ, Papadakis MA, Tierney LM (ed).

Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition

The McGraw-Hill Companies, Inc. (2007)