Microsomal Prostaglandin E2 Synthase-1 as a New Macromolecular Drug Target in the Prevention of İnflammation and Cancer.

BACKGROUND: Cancer is one of the top killing disease worldwide. Since inflammation is considered to be one of the known characteristics of cancer, the activity of PGE2 has been paired with different tumorigenetic steps such as increased tumor cell proliferation, resistance to apoptosis, increased invasiveness, angiogenesis and immunosuppression.

OBJECTIVE: It has been succesfully demonstrated that inhibition of mPGES-1 prevented inflammation in preclinical studies. However, despite the important roles of mPGEs-1 and PGE2 in tumorigenesis, there is not much in vivo study on mPGES-1 inhibition in cancer therapy. The specificity of mPGEs-1 enzyme and its low expression level under normal conditions makes it a promising drug target with a low risk of side effects.

METHOD: A comprehensive literature search was performed for writing this review. An updated view on PGE2 biosynthesis, PGES isoenzyme family and its pharmacology and the latest information about inhibitors of mPGES-1 have been discussed.

RESULTS: In this study it was aimed to highlight the importance of mPGES-1 and its inhibition in inflammation related cancer and other inflammatory conditions. Information about PGE2 biosynthesis, it's role in inflammation related pathologies were also provided. We kept the noncancer related inflammatory part short and tried to bring together promising molecules or scaffolds.

CONCLUSION: The information provided in this review might be useful to researchers in designing of novel and potent mPGES-1 inhibitors for the treatment of cancer and inflammation.