Digestive Molecular Clinical Oncology Research Unit , Section of Medical Oncology, Department of Medicine, University of Verona, Verona, Italy.
Expert Opin Ther Targets. 2012 Apr;16 Suppl 2:S1-10. doi: 10.1517/14728222.2011.645806. Epub 2012 Mar 23.
Pancreatic cancer is the fourth leading cause of adult cancer mortality in the USA. It represents one of the greatest challenges in cancer treatment. The NF-κB transcriptional factors are constitutively activated in the majority of pancreatic cancers and are involved in the regulation of numerous aspects of tumor development and progression. NF-κB and the signaling cascades that regulate its activity have thus become attractive targets for novel therapeutic approaches for pancreatic cancer.
This review describes and discusses the most important advances in the comprehension of the complex molecular biology of NF-κB, as well as the development of novel NF-κB-targeting strategies for the treatment of pancreatic cancer.
Although the inhibition of NF-κB, especially when combined with more classic chemotherapeutic drugs, could be a promising therapeutic strategy, direct targeting NF-κB still faces important challenges. In the future, targeting nonredundant cytosolic mediators of the activation of NF-κB - such as TNF receptor associated factor family member-associated NF-κB activator -binding kinase 1 (TBK1) and TGF-beta activated kinase 1 (TAK1) - could represent a better approach to inhibit key processes in pancreatic tumor cells and make a difference for this devastating disease.
在美国，胰腺癌是导致成年人癌症死亡的第四大主要原因。它是癌症治疗中最大的挑战之一。大多数胰腺癌中 NF-κB 转录因子持续激活，并参与肿瘤发生和进展的多个方面的调节。因此，NF-κB 及其调节其活性的信号级联已成为治疗胰腺癌的新型治疗方法的有吸引力的靶点。
本文描述和讨论了对 NF-κB 复杂分子生物学的理解以及针对治疗胰腺癌的新型 NF-κB 靶向策略的最重要进展。
尽管抑制 NF-κB（尤其是与更经典的化疗药物联合使用时）可能是一种很有前途的治疗策略，但直接靶向 NF-κB 仍面临重要挑战。未来，针对 NF-κB 激活的非冗余胞质介质，如 TNF 受体相关因子家族成员相关 NF-κB 激活剂结合激酶 1（TBK1）和转化生长因子-β激活激酶 1（TAK1），可能是抑制胰腺肿瘤细胞关键过程的更好方法，并为这种毁灭性疾病带来改变。
