Department of Basic Sciences, Kentucky College of Osteopathic Medicine, University of Pikeville, Pikeville, KY 41501, USA.
Department of Physiology, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Int J Mol Sci. 2018 Dec 5;19(12):3890. doi: 10.3390/ijms19123890.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers and is the third highest among cancer related deaths. Despite modest success with therapy such as gemcitabine, pancreatic cancer incidence remains virtually unchanged in the past 25 years. Among the several driver mutations for PDAC, mutation contributes a central role for its development, progression and therapeutic resistance. In addition, inflammation is implicated in the development of most human cancer, including pancreatic cancer. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is recognized as a key mediator of inflammation and has been frequently observed to be upregulated in PDAC. Several lines of evidence suggest that NF-κB pathways play a crucial role in PDAC development, progression and resistance. In this review, we focused on emphasizing the recent advancements in the involvement of NF-κB in PADC's progression and resistance. We also highlighted the interaction of NF-κB with other signaling pathways. Lastly, we also aim to discuss how NF-κB could be an excellent target for PDAC prevention or therapy. This review could provide insight into the development of novel therapeutic strategies by considering NF-κB as a target to prevent or treat PDAC.
胰腺导管腺癌（PDAC）是最致命的癌症之一，也是癌症相关死亡的第三大原因。尽管在吉西他滨等治疗方面取得了一定的成功，但在过去的 25 年中，胰腺癌的发病率几乎没有变化。在 PDAC 的几个驱动突变中， 突变在其发展、进展和治疗耐药性中起着核心作用。此外，炎症与大多数人类癌症的发生有关，包括胰腺癌。核因子κB 轻链增强子的激活 B 细胞（NF-κB）被认为是炎症的关键介质，并且在 PDAC 中经常观察到其上调。有几条证据表明，NF-κB 途径在 PDAC 的发展、进展和耐药性中起着至关重要的作用。在这篇综述中，我们重点强调了 NF-κB 在 PADC 进展和耐药性中的最新研究进展。我们还强调了 NF-κB 与其他信号通路的相互作用。最后，我们还旨在讨论 NF-κB 如何成为 PDAC 预防或治疗的一个极好的靶点。通过将 NF-κB 视为预防或治疗 PDAC 的靶点，本综述可以为开发新的治疗策略提供思路。
