Jackson Lindsey, Evers B Mark
Department of Surgery, The University of Texas Medical Branch Galveston, Texas, USA.
Cancer Treat Res. 2006;130:39-65. doi: 10.1007/0-387-26283-0_2.
The pathogenesis of cancer represents a complex and multifactorial process requiring a number of acquired and genetic defects. It is becoming increasingly apparent that many cancers originate from a chronic inflammatory process. The topic of this review is the inflammatory response and development of gastrointestinal (GI) and pancreatic cancers. Here, we describe the development of various gastric colorectal and pancreatic cancers through an inflammatory process. The tumor microenvironment which predisposes to tissue destruction, subsequent attempts at healing and accumulation of cellular damage with loss of cell cycle control mechanisms is discussed. Components of the tumor microenvironment that are important in the final common pathway leading to cancer include the tumor stroma, tumor-associated macrophages, cytokines and chemokines and reactive oxygen and nitrogen species. Common signaling pathways that link inflammation with cancer are described and include the COX-2, NF-kappaB and phosphatidyl inositol 3-kinase (PI3K) pathways. Finally, therapies that can be directed to the inflammatory process as either treatment or prevention of these cancers will be discussed including novel inhibitors of signaling pathways which are currently in development.
癌症的发病机制是一个复杂的多因素过程，需要多种后天性和遗传性缺陷。越来越明显的是，许多癌症起源于慢性炎症过程。本综述的主题是胃肠道（GI）癌和胰腺癌的炎症反应与发展。在此，我们描述了各种胃癌、结直肠癌和胰腺癌通过炎症过程的发展。我们还讨论了肿瘤微环境，它易引发组织破坏，随后是愈合尝试以及细胞损伤的积累，并伴有细胞周期控制机制的丧失。在导致癌症的最终共同途径中起重要作用的肿瘤微环境成分包括肿瘤基质、肿瘤相关巨噬细胞、细胞因子、趋化因子以及活性氧和氮物种。文中描述了将炎症与癌症联系起来的常见信号通路，包括COX - 2、核因子κB（NF - κB）和磷脂酰肌醇3 -激酶（PI3K）通路。最后，将讨论可针对炎症过程用于治疗或预防这些癌症的疗法，包括目前正在研发的新型信号通路抑制剂。
