title: [Advance in the biology of pancreatic of cancer].
abstract: The understanding of the biology of pancreatic carcinoma has greatly benefited from studies of genetic/epigenetic alterations and molecular expression in experimental models as well as precancerous and cancerous tissues by mean of molecular amplification and large-scale transcriptoma analysis. P16, TP53, DPC4/Smad4 tumor suppressor pathways are genetically inactivated in the majority of pancreatic carcinomas, whereas oncogenic k-ras is activated. The activating point mutation of the KRAS oncogene on codon 12 is the major event and occurs early in pancreatic carcinogenesis. At a late stage of tumor development, an increase of telomerase activity, an over expression of growth factors and/or their receptors (EGF, Nerve Growth Factor, gastrin), of pro-angiogenic factors (VEGF, FGF, PDGF), of invasiveness factors (metalloproteinases, tissue plasminogen activators) occurs. The microenvironment plays also a key role in the invasive and metastatic process of pancreatic carcinoma with a strong relationship between cancerous cells and pancreatic stellate cells as well as extracellular matrix. This microenvironment strongly participates to the tumor fibrosis, hypoxia and hypovascularization inducing an inaccessibility of drugs. Nowadays, the targeting of microenvironment takes a special place in the new therapeutic strategies of pancreatic cancer in combination with chemotherapy.
authors.affiliation: Inserm UMR 1037, Centre de recherche en cancérologie de Toulouse 2, avenue Hubert-Curien, Oncopole de Toulouse, CS 53717, 31037 Toulouse cedex 1. Electronic address: Buscail.L@chu-toulouse.fr.
authors.forename: Louis
authors.initials: L
authors.lastname: Buscail
authors.affiliation: Inserm UMR 1037, Centre de recherche en cancérologie de Toulouse 2, avenue Hubert-Curien, Oncopole de Toulouse, CS 53717, 31037 Toulouse cedex 1.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bournet
authors.affiliation: Inserm UMR 1037, Centre de recherche en cancérologie de Toulouse 2, avenue Hubert-Curien, Oncopole de Toulouse, CS 53717, 31037 Toulouse cedex 1.
authors.forename: Marlène
authors.initials: M
authors.lastname: Dufresne
authors.affiliation: Inserm UMR 1037, Centre de recherche en cancérologie de Toulouse 2, avenue Hubert-Curien, Oncopole de Toulouse, CS 53717, 31037 Toulouse cedex 1.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Torrisani
authors.affiliation: Inserm UMR 1037, Centre de recherche en cancérologie de Toulouse 2, avenue Hubert-Curien, Oncopole de Toulouse, CS 53717, 31037 Toulouse cedex 1.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cordelier
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019512:Pancreatitis, Alcoholic / Q000150:complications; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D019098:Telomerase / Q000378:metabolism; D059016:Tumor Microenvironment; D018631:ras Proteins / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019098:Telomerase; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Cancer du pancréas; Cibles thérapeutiques; Epigenetics; Microenvironment; Microenvironnement; Molecular therapeutic; Moléculaires; Pancreatic ductal; adenocarcinoma; exocrine; targets; Épigénétique