Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Mol Carcinog. 2012 Jan;51(1):25-39. doi: 10.1002/mc.20827.
Pancreatic cancer is a devastating disease with historically limited success in treatment and a poor prognosis. Pancreatic cancer appears to have a progressive pathway of development, initiating from well-described pancreatic intraepithelial neoplasia lesions and concluding with invasive carcinoma. These early lesions have been shown to harbor-specific alterations in signaling pathways that remain throughout this tumorigenesis process. Meanwhile, new alterations occur during this process of disease progression to have a cumulative effect. This series of events not only impacts the epithelial cells comprising the tumor, but they may also affect the surrounding stromal cells. The result is the formation of complex signaling networks of communication between the tumor epithelial cell and the stromal cell compartments to promote a permissive and cooperative environment. This article highlights some of the most common pathway aberrations involved with this disease, and how these may subsequently affect one or both cellular compartments. Consequently, furthering our understanding of these pathways in terms of their function on the tumoral epithelial and stromal compartments may prove to be crucial to the development of targeted and more successful therapies in the future.
胰腺癌是一种具有破坏性的疾病，在治疗方面历史上收效甚微，预后不良。胰腺癌似乎具有一个渐进的发展途径，从描述明确的胰腺上皮内瘤变病变开始，并以浸润性癌结束。这些早期病变表现出在信号通路中存在特定的改变，这些改变在整个肿瘤发生过程中仍然存在。同时，在疾病进展过程中会发生新的改变，从而产生累积效应。这一系列事件不仅影响构成肿瘤的上皮细胞，还可能影响周围的基质细胞。结果是肿瘤上皮细胞和基质细胞之间形成了复杂的信号网络交流，以促进一个许可和合作的环境。本文重点介绍了一些与这种疾病相关的最常见的途径异常，以及这些途径如何随后影响一个或两个细胞区室。因此，进一步了解这些途径在肿瘤上皮和基质区室中的功能可能对未来开发靶向和更成功的治疗方法至关重要。
