World J Gastroenterol. 2012 Apr 7;18(13):1417-24. doi: 10.3748/wjg.v18.i13.1417.
Despite improvements in surgical techniques and adjuvant chemotherapy, the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%. This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes, proteins, microRNAs or epigenetic modifications. However, there are still major hurdles when translating investigational biomarkers into routine clinical practice. Furthermore, novel ways of secondary screening in high-risk individuals, such as artificial neural networks and modern imaging, will be discussed. Drug resistance is ubiquitous in pancreatic cancer. Several mechanisms of drug resistance have already been revealed, including human equilibrative nucleoside transporter-1 status, multidrug resistance proteins, aberrant signaling pathways, microRNAs, stromal influence, epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells. These factors must be considered when developing more customized types of intervention ("personalized medicine"). In the future, multifunctional nanoparticles that combine a specific targeting agent, an imaging probe, a cell-penetrating agent, a biocompatible polymer and an anti-cancer drug may become valuable for the management of patients with pancreatic cancer.
尽管手术技术和辅助化疗有所改进,但胰腺癌的总体死亡率总体上仍相对不变,5 年生存率实际上低于 2%。本文将讨论早期诊断的重要性,并确定用于预后和治疗反应的标志物,如基因、蛋白质、microRNAs 或表观遗传修饰。然而,将研究性生物标志物转化为常规临床实践仍然存在重大障碍。此外,还将讨论用于高危人群的二次筛选的新方法,如人工神经网络和现代成像。胰腺癌普遍存在耐药性。已经揭示了几种耐药机制,包括人平衡核苷转运蛋白-1 状态、多药耐药蛋白、异常信号通路、microRNAs、基质影响、上皮-间充质转化型细胞以及最近存在的癌症干细胞/起始细胞。在开发更具针对性的干预措施(“个性化医学”)时,必须考虑这些因素。未来,将特定靶向剂、成像探针、细胞穿透剂、生物相容聚合物和抗癌药物结合在一起的多功能纳米粒子可能对管理胰腺癌患者具有重要价值。