Nuclear factor-kappaB in development, prevention, and therapy of cancer.

Abstract

Nuclear factor-kappaB (NF-kappaB) is a signal transcription factor that has emerged as an important modulator of altered gene programs and malignant phenotype in development of cancer. Major carcinogens and oncogenic viruses induce NF-kappaB activation, and a variety of subsequent oncogenic events contribute to a progressive increase in constitutive NF-kappaB activation as an important common pathway in most forms of cancer. NF-kappaB target genes promote tumor cell proliferation, survival, migration, inflammation, and angiogenesis. Inhibition of NF-kappaB has been found to be an important mechanism of action of steroids, nonsteroidal anti-inflammatory drugs, and natural and synthetic compounds that show therapeutic and preventive activity. Newer agents targeting the proteasome, inhibitor-kappaB kinase, and other upstream kinases involved in NF-kappaB activation have shown anticancer activity in clinical or preclinical studies.