Nuclear factor-kappa B: From clone to clinic

Nuclear transcription factor B (NF-kappa B) was first discovered in 1986 in the nucleus of the B cell as an enhancer in the immunoglobulin chain. However, this factor has identified in the cytoplasm in the resting state. When activated in response to inflammatory stimuli, carcinogens, stress, ionizing radiation, and growth factors; NF-kappa B translocates to the nucleus where it upregulates the expression of over 400 different gene products linked with inflammation, cell survival, proliferation, invasion, and angiogenesis. The activation of NF-kappa B has now been linked with a variety of inflammatory diseases, including cancer and pulmonary, autoimmune, skin, neurodegenerative, and cardiovascular disorders. Indeed, constitutive NF-kappa B activation frequently correlates with the proliferation, survival, chemoresistance, radioresistance, and progression of various cancers. Hence, NF-kappa B has both diagnostic and prognostic applications. In addition, pharmaceutical companies are aggressively pursuing development of inhibitors of NF-kappa B with therapeutic potential. Thus within last decades this transcription factor, discovered serendipitously, has moved from clone to clinic.