Prostaglandin E2 Receptor 4 (EP4): A Promising Therapeutic Target for the Treatment of Cancer and Inflammatory Diseases

Abstract

Prostaglandin E2 (PGE2) is involved in several biological processes, including inflammation, pain, fever, renal function, mucosal integrity, angiogenesis and tumor growth. PGE2 receptor subtypes (EP1-4) play pivotal roles in PGE2-mediated biological events. Recent studies revealed the fact that EP4 is commonly upregulated in cancer to stimulate cell proliferation, migration, invasion, and metastasis. Additionally, the EP4 receptor has a role in several anti-inflammatory processes, bone formation and hemostasis. EP4 receptor modulators can be used as drugs of specific interest. A number of EP4 receptor agonists and antagonists are at different stages of clinical development. The agonists of EP4 receptor showed promising results for ulcerative colitis (UC), bone deposition and facilitated bone resorption. The uses of EP4 antagonists, particularly in combination with chemotherapy, endocrine therapy, or immune-based therapies, may be the treatment options for cancer. Several EP4 antagonists are being progressed in clinical trials and hopefully, the results will show the usefulness of EP4 receptor as a target for cancer therapeutics. In this review, we have summarized the EP4 receptor and the possible therapeutic applications of EP4 receptor- selective agonists and antagonists.