Increasing evidence from epidemiological,
preclinical and clinical studies suggests that dysregulated inflammatory
response plays a pivotal role in a multitude of chronic ailments including
cancer. The molecular mechanism(s) by which chronic inflammation drives cancer
initiation and promotion include increased production of pro-inflammatory
mediators, such as cytokines, chemokines, reactive oxygen intermediates,
increased expression of oncogenes, COX-2 (cyclo-oxygenase-2), 5-LOX
(5-lipoxygenase) and MMPs (matrix metalloproteinases), and pro-inflammatory
transcription factors such as NF-κB (nuclear factor κB), STAT3 (signal
transducer and activator of transcription 3), AP-1 (activator protein 1) and
HIF-1α (hypoxia-inducible factor 1α) that mediate tumour cell proliferation,
transformation, metastasis, survival, invasion, angiogenesis, chemoresistance
and radioresistance. These inflammation-associated molecules are activated by a
number of environmental and lifestyle-related factors including infectious
agents, tobacco, stress, diet, obesity and alcohol, which together are thought
to drive as much as 90% of all cancers. The present review will focus primarily
on the role of various inflammatory intermediates responsible for tumour
initiation and progression, and discuss in detail the critical link between
inflammation and cancer.
