The nuclear factor kappa-B signaling pathway as a therapeutic target against thyroid cancers

The nuclear factor kappa-B (NF-κB) proteins, a family of transcription factors found virtually in all cells, are known to play crucial roles in the growth of a number of human malignancies. The ability of NF-κB to target a large number of genes that regulate cell proliferation, differentiation, survival, and apoptosis, provides clues toward its deregulation during the process of tumorigenesis, metastatic progression, and therapeutic resistance of tumors.

In addition to the signaling pathways known to be involved in thyroid tumorigenesis, such as the mitogen-activated protein kinase and janus kinase cascades, studies implicate the NF-κB pathway in the development of both less aggressive thyroid cancers, papillary and follicular adenocarcinomas, and progression to aggressive thyroid cancers, such as anaplastic adenocarcinomas. A constitutively activated NF-κB pathway also closely links Hashimoto's thyroiditis with increased incidence of thyroid cancers. The NF-κB pathway is becoming one of the major targets for drug development, and a number of compounds have been developed to inhibit this pathway at different levels in cancer cells. Some of these targets have shown promising outcomes in both in vitro and in vivo investigations and a handful of them have shown efficacy in the clinical setting.

This review discusses the recent findings that demonstrate that the inhibition of NF-κB, alone or with other signaling pathway inhibitors may be of significant therapeutic benefits against aggressive thyroid cancers.