NF-κB and Human Cancer: What Have We Learned over the Past 35 Years?

Transcription factor NF-kappa B has been extensively studied for its varied roles in cancer development since its initial characterization as a potent retroviral oncogene. It is now clear that NF-kappa B also plays a major role in a large variety of human cancers, including especially ones of immune cell origin. NF-kappa B is generally constitutively or aberrantly activated in human cancers where it is involved. These activations can occur due to mutations in the NF-kappa B transcription factors themselves, in upstream regulators of NF-kappa B, or in pathways that impact NF-kappa B. In addition, NF-kappa B can be activated by tumor-assisting processes such as inflammation, stromal effects, and genetic or epigenetic changes in chromatin. Aberrant NF-kappa B activity can affect many tumor-associated processes, including cell survival, cell cycle progression, inflammation, metastasis, angiogenesis, and regulatory T cell function. As such, inhibition of NF-kappa B has often been investigated as an anticancer strategy. Nevertheless, with a few exceptions, NF-kappa B inhibition has had limited success in human cancer treatment. This review covers general themes that have emerged regarding the biological roles and mechanisms by which NF-kappa B contributes to human cancers and new thoughts on how NF-kappa B may be targeted for cancer prognosis or therapy.