Although
inflammation has long been known as a localized protective reaction of tissue to irritation, injury, or
infection, characterized by
pain, redness, swelling, and sometimes loss of function, there has been a new realization about its role in a wide variety of diseases, including
cancer. While acute
inflammation is a part of the defense response, chronic
inflammation can lead to
cancer, diabetes, cardiovascular, pulmonary, and neurological diseases. Several pro-inflammatory gene products have been identified that mediate a critical role in suppression of apoptosis, proliferation, angiogenesis, invasion, and
metastasis. Among these gene products are TNF and members of its superfamily, IL-1alpha, IL-1beta,
IL-6,
IL-8,
IL-18,
chemokines, MMP-9,
VEGF, COX-2, and 5-LOX. The expression of all these genes are mainly regulated by the
transcription factor NF-kappaB, which is constitutively active in most
tumors and is induced by
carcinogens (such as cigarette
smoke),
tumor promoters, carcinogenic
viral proteins (HIV-tat, HIV-nef, HIV-vpr, KHSV, EBV-LMP1, HTLV1-tax, HPV, HCV, and HBV), chemotherapeutic agents, and gamma-irradiation. These observations imply that
anti-inflammatory agents that suppress
NF-kappaB or
NF-kappaB-regulated products should have a potential in both the prevention and treatment of
cancer. The current review describes in detail the critical link between
inflammation and
cancer.