Inflammation in the tumor microenvironment is now recognized as one of the hallmarks of
cancer. Endogenously produced
lipid autacoids, locally acting small molecule
lipid mediators, play a central role in
inflammation and tissue homeostasis, and have recently been implicated in
cancer. A well-studied group of
autacoid mediators that are the products of
arachidonic acid metabolism include: the
prostaglandins,
leukotrienes,
lipoxins and
cytochrome P450 (CYP) derived bioactive products. These
lipid mediators are collectively referred to as
eicosanoids and are generated by distinct enzymatic systems initiated by
cyclooxygenases (COX 1 and 2),
lipoxygenases (5-LOX, 12-LOX, 15-LOXa, 15-LOXb), and
cytochrome P450s, respectively. These pathways are the target of approved drugs for the treatment of
inflammation,
pain,
asthma,
allergies, and cardiovascular disorders. Beyond their potent anti-inflammatory and anti-
cancer effects, non-steroidal anti-inflammatory drugs (
NSAIDs) and COX-2 specific inhibitors have been evaluated in both preclinical
tumor models and clinical trials.
Eicosanoid biosynthesis and actions can also be directly influenced by nutrients in the diet, as evidenced by the emerging role of
omega-3 fatty acids in
cancer prevention and treatment. Most research dedicated to using
eicosanoids to inhibit
tumor-associated
inflammation has focused on the COX and LOX pathways. Novel experimental approaches that demonstrate the anti-
tumor effects of inhibiting
cancer-associated
inflammation currently include:
eicosanoid receptor antagonism, overexpression of
eicosanoid metabolizing
enzymes, and the use of endogenous anti-inflammatory
lipid mediators. Here we review the actions of
eicosanoids on
inflammation in the context of
tumorigenesis.
Eicosanoids may represent a missing link between
inflammation and
cancer and thus could serve as therapeutic target(s) for inhibiting
tumor growth.