泌尿器系癌におけるEプロスタノイドレセプターとその役割

Abstract

The biological activities of prostaglandin E2 are mediated through their specific receptors, E prostanoid receptors (EPRs). This family comprises 4 subtypes (EP1R-4R), and has been associated with cancer development and progression. In urological cancers, expression of EP2R and EP4R can be significant predictors of survival for renal cell carcinoma (RCC). On the other hand, EP1R, EP2R, and EP4R are known to be associated with carcinogenesis and malignant aggressiveness in prostate cancer. In addition, EP4R has been associated with tumor progression and prognosis in urothelial cancer of the upper urinary tract. There is a general agreement that non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of several malignancies including colorectal cancer. However, NSAIDs often cause gastrointestinal injury and nephropathy. On the other hand, cyclooxygenase (COX)-2-selective inhibitors can reduce the progression of cancer via the suppression of cell proliferation angiogenesis without decreasing adverse reactions. However, COX-2-selective inhibitors might increase the risk of cardiovascular disease, including myocardial infarction. More selective and detailed control of COX-2-mediated signals is thus needed to improve anti-tumor effects and to decrease adverse reactions. EPRs are expected to serve as new therapeutic targets in urological cancer, because they are more selective in malignant phenotypes. Finally, we speculate that some EPRs inhibitors may reduce adverse events and exert more intense effects on urological cancer.