Jimeno Antonio, Hidalgo Manuel
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Room 1M88, 1650 Orleans Street, Baltimore, MD 21231-1000, USA.
Mol Cancer Ther. 2006 Apr;5(4):787-96. doi: 10.1158/1535-7163.MCT-06-0005.
The rapidly expanding knowledge of the pathogenesis of pancreatic cancer at the molecular level is providing new targets for disease characterization, early diagnosis, and drug discovery and development. Gene mutation analysis has provided insight on the pathogenesis and progression from preinvasive lesions to invasive cancer. Gene and protein expression profiling has advanced our understanding of pancreatic ductal adenocarcinoma identifying genes that are highly expressed in pancreatic cancers, providing more insight into the clinicopathologic features of pancreatic cancer, and revealing novel features related to the process of tissue invasion by these tumors. The increasing knowledge of the pathway activation profile in pancreatic cancer is yielding new targets but also new markers to select patients and guide and predict therapy efficacy. The discovery of genetic factors of which the presence predisposes pancreatic cancer to successful targeting, such as the association of BRCA2/Fanconi anemia genes defects and sensitivity to mitomycin C, will eventually lead to a more individualized treatment approach. In summary, several decades of intensive research have originated multiple factors or biomarkers that are likely to be helpful in the diagnosis, characterization, and therapy selection of pancreatic cancer patients. A deep understanding of the relative relevance of each biomarker will be key to efficiently diagnose this disease and direct our patients towards the drugs more likely to be of benefit based on their particular profile. The development of new preclinical models is of paramount importance to achieve these goals.
在分子水平上，人们对胰腺癌发病机制的认识迅速扩展，这为疾病特征描述、早期诊断以及药物研发提供了新的靶点。基因突变分析为从癌前病变到浸润性癌的发病机制及进展提供了见解。基因和蛋白质表达谱分析加深了我们对胰腺导管腺癌的理解，确定了在胰腺癌中高表达的基因，为胰腺癌的临床病理特征提供了更多见解，并揭示了与这些肿瘤组织侵袭过程相关的新特征。对胰腺癌中信号通路激活谱的了解不断增加，不仅产生了新的靶点，还产生了用于选择患者、指导和预测治疗效果的新标志物。发现某些遗传因素的存在使胰腺癌易于成功靶向治疗，例如BRCA2/范可尼贫血基因缺陷与对丝裂霉素C的敏感性之间的关联，最终将导致更个体化的治疗方法。总之，几十年的深入研究产生了多种可能有助于胰腺癌患者诊断、特征描述和治疗选择的因素或生物标志物。深入了解每种生物标志物的相对相关性，对于有效诊断这种疾病并根据患者的特定情况指导他们使用更可能有益的药物至关重要。开发新的临床前模型对于实现这些目标至关重要。
