Recent studies have shown overexpression of cyclooxygenase 2 (COX 2) and 5-lipoxygenase (5-lipox) in exocrine pancreatic carcinomas, suggesting a potential role of the arachidonic acid (AA) cascade in the regulation of this cancer type.
This targeting method was then used to direct the expression of inducible forms of caspases 3 and 9 to Cox-2-overexpressing cancer cells of the bladder and prostate.
We propose that pretreatment with selective Cox-2 inhibitors may be useful in the prevention of multidrug resistance in response to cancer chemotherapy and should be further evaluated.
The main current treatments against platelets are: (1) acetylsalicylic acid (aspirin) and nonsteroidal anti-inflammatory drugs, nonselective cyclo-oxygenase (COX)-1 and COX-2 inhibitors, which are associated with decreased cancer incidence and better overall survival and (2) irreversible inhibitor of P2Y12 subtype which decreases cancer incidence.
Global expression profiling initially found gastric tumors from COX-2/mPGES-1 (C2mE)-related transgenic mice (K19-C2mE, K19-Wnt1/C2mE, and K19-Nog/C2mE) resembled gastric cancers among the several tissues of human cancers including colon, breast, lung and gastric tumors.
Several lines of evidence suggest that the cyclooxygenase enzymes (specifically COX-2) might be an important molecular target for the intervention of cancer at both early and late stages of some cancers, providing an opportunity for both cancer prevention and therapy.
Levels of COX-2 mRNA are found over-expressed in almost 80% of the colorectal tumors, compared to paired adjacent normal colorectal mucosa, suggesting a role of COX-2 as a potential biomarker for cancer risk, whereas inhibitors of COX-2 could be of value in chemoprevention of colon cancer.
Prostaglandins serve as the connecting link between inflammation and cancer. mPGES1, the downstream enzyme in the prostaglandin pathway is considered a better target than COX-2 against the progression of cancer due to the cardiovascular and other complications associated with the inhibition of the latter.
The biological significance of such checkpoint control may account for COX-2-dependent mechanisms of inflammatory balance responsible of therapy resistance phenotype of cancer stem cells.
Indometacin, a well‑known anti‑inflammatory drug and a non‑selective inhibitor of COX‑2, has been shown to exert anticancer effects in various types of cancer, including PDAC.
Whereas COX-2 and PGE(2) are associated with cancer cell survival and tumor angiogenesis, arachidonic acid itself is a strong apoptotic signal that may facilitate cancer cell death.
Non-small-cell lung cancer (NSCLC), especially adenocarcinomas, overexpress COX-2, which contributes to the progression of malignancy by several mechanisms.
Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention.