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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.
摘要：
通过分子扩增和大规模转录瘤分析，对实验模型以及癌前组织和癌组织中的遗传/表观遗传改变和分子表达的研究极大地受益于对胰腺癌生物学的理解。P16，TP53，DPC4/Smad4肿瘤抑制途径在大多数胰腺癌中被基因灭活，而致癌k-ras被激活。KRAS癌基因第12密码子的激活点突变是主要事件，发生在胰腺癌发生的早期。在肿瘤发展的晚期，端粒酶活性的增加，生长因子和/或其受体的过度表达(EGF，神经生长因子,胃泌素)，促血管生成因子(VEGF，FGF,PDGF),侵袭因子(金属蛋白酶，组织纤溶酶原激活物）发生。微环境在胰腺癌的侵袭和转移过程中也起着关键作用，癌细胞与胰腺星状细胞以及细胞外基质之间存在着密切的关系。这种微环境强烈参与肿瘤纤维化，缺氧和血管形成不足导致药物难以接近。如今,靶向微环境在胰腺癌联合化疗的新治疗策略中占有特殊地位.
