Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Bharat B AggarwalBokyung Sung

Abstract

Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most common types of cancer. All these risk factors are linked to cancer through inflammation. Although acute inflammation that persists for short-term mediates host defense against infections, chronic inflammation that lasts for long term can predispose the host to various chronic illnesses, including cancer. Linkage between cancer and inflammation is indicated by numerous lines of evidence; first, transcription factors nuclear factor-kappaB (NF-kappaB) and signal transducers and activators of transcription 3 (STAT3), two major pathways for inflammation, are activated by most cancer risk factors; second, an inflammatory condition precedes most cancers; third, NF-kappaB and STAT3 are constitutively active in most cancers; fourth, hypoxia and acidic conditions found in solid tumors activate NF-kappaB; fifth, chemotherapeutic agents and gamma-irradiation activate NF-kappaB and lead to chemoresistance and radioresistance; sixth, most gene products linked to inflammation, survival, proliferation, invasion, angiogenesis, and metastasis are regulated by NF-kappaB and STAT3; seven...Continue Reading

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