Cooperation between Prostaglandin E2 and Epidermal Growth Factor Receptor in Cancer Progression: A Dual Target for Cancer Therapy

SIMPLE SUMMARY: Inflammation is the biological response of the body to damaging and toxic stimuli, and is a positive event that evolves with the resolution of critical events (acute inflammation). However, when the process becomes chronic it acquires pathological characteristics, and is associated with detrimental diseases such as cancer. It is recognized that prostaglandin E2 (PGE2) is one key lipid mediator involved in chronic inflammation, and is directly implicated in tumor development by regulating cancer cell growth and migration, apoptosis, epithelial–mesenchymal transition, metastasis, angiogenesis, and immune escape. The enzymes’ expression in PGE2 synthesis positively correlates with tumor progression and aggressiveness. This review describes the interplay between the PGE2 cascade and epidermal growth factor receptor that fuel cancer progression, and new therapeutic strategies that target these signaling pathways, to outline the importance of the modulation of the inflammatory process in cancer fighting. ABSTRACT: It is recognized that prostaglandin E2 (PGE2) is one key lipid mediator involved in chronic inflammation, and it is directly implicated in tumor development by regulating cancer cell growth and migration, apoptosis, epithelial–mesenchymal transition, angiogenesis, and immune escape. In addition, the expression of the enzymes involved in PGE2 synthesis, cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES1), positively correlates with tumor progression and aggressiveness, clearly indicating the crucial role of the entire pathway in cancer. Moreover, several lines of evidence suggest that the COX2/mPGES1/PGE2 inflammatory axis is involved in the modulation of epidermal growth factor receptor (EGFR) signaling to reinforce the oncogenic drive of EGFR activation. Similarly, EGFR activation promotes the induction of COX2/mPGES1 expression and PGE2 production. In this review, we describe the interplay between COX2/mPGES1/PGE2 and EGFR in cancer, and new therapeutic strategies that target this signaling pathway, to outline the importance of the modulation of the inflammatory process in cancer fighting.