It is widely accepted that many
cancers express features of
inflammation, driven by both microenvironmental cells and factors, and the intrinsic production of
inflammation-associated mediators from malignant cells themselves.
Inflammation results in intracellular oxidative stress with the ultimate biochemical
oxidants composed of reactive nitrogens and oxygens. Although the role of
inflammation in carcinogensis is well accepted, we now present data showing that inflammatory processes are also active in the maintenance phase of many aggressive forms of
cancer. The oxidative stress of
inflammation is proposed to drive a continuous process of
DNA adducts and crosslinks, as well as posttranslational modifications to
lipids and
proteins that we argue support growth and survival. In this perspective, we introduce data on the emerging science of
inflammation-driven posttranslational modifications on
proteins responsible for driving growth, angiogenesis, immunosuppression, and inhibition of apoptosis. Examples include data from human
melanoma, breast, head and neck, lung, and
colon cancers. Fortunately, numerous
antioxidant agents are clinically available, and we further propose that the pharmacologic attenuation of these inflammatory processes, particularly the
reactive nitrogen species, will restore the
cancer cells to an apoptosis-permissive and growth-inhibitory state. Our mouse model data using an
arginine antagonist that prevents enzymatic production of
nitric oxide directly supports this view. We contend that selected
antioxidants be considered as part of the
cancer treatment approach, as they are likely to provide a novel and mechanistically justified addition for therapeutic benefit.