Prostaglandin E Receptor 4 Antagonist in Cancer Immunotherapy: Mechanisms of Action.

A highly expressed prostaglandin E (PGE) in tumor tissues suppresses antitumor immunity in the tumor microenvironment (TME) and causes tumor immune evasion leading to disease progression. In animal studies, selective inhibition of the prostaglandin E receptor 4 (EP4), one of four PGE receptors, suppresses tumor growth, restoring the tumor immune response toward an antitumorigenic condition. This review summarizes PGE/EP4 signal inhibition in relation to the cancer-immunity cycle (C-IC), which describes fundamental tumor-immune interactions in cancer immunotherapy.

Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility.

Tegoprazan [()-4-((5,7-difluorochroman-4-yl)oxy)-,,2-trimethyl-1-benzo[d]imidazole-6-carboxamide], a potassium-competitive acid blocker (P-CAB), is a novel potent and highly selective inhibitor of gastric H/K-ATPase. Tegoprazan inhibited porcine, canine, and human H/K-ATPases in vitro with IC values ranging from 0.29 to 0.

Prostaglandin E receptor EP4 is a therapeutic target in breast cancer cells with stem-like properties.

The cyclooxygenase pathway is strongly implicated in breast cancer progression but the role of this pathway in the biology of breast cancer stem/progenitor cells has not been defined. Recent attention has focused on targeting the cyclooxygenase 2 (COX-2) pathway downstream of the COX-2 enzyme by blocking the activities of individual prostaglandin E (EP) receptors. Prostaglandin E receptor 4 (EP4) is widely expressed in primary invasive ductal carcinomas of the breast and antagonizing this receptor with small molecule inhibitors or shRNA directed to EP4 inhibits metastatic potential in both syngeneic and xenograft models.

A prostaglandin E (PGE) receptor EP4 antagonist protects natural killer cells from PGE-mediated immunosuppression and inhibits breast cancer metastasis.

Cyclooxygenase-2 is frequently upregulated in epithelial tumors and contributes to poor outcomes in multiple malignancies. The COX-2 product prostaglandin E (PGE) promotes tumor growth and metastasis by acting on a family of four G protein-coupled receptors (EP1-4). Using a novel small molecule EP4 antagonist (RQ-15986) and a syngeneic murine model of metastatic breast cancer, we determined the effect of EP4 blockade on innate immunity and tumor biology.