The PGE2-EP Receptor Axis in Colorectal Cancer and Angiogenesis

Abstract

Colorectal Cancer is the third most common cause of cancer-related mortality worldwide with rapidly increasing incidence. Substantial evidence suggests that elevated PGE2 expression, frequently observed in colorectal tumours, enables development of a number of cancer hallmarks, including angiogenesis, which is initiated relatively early in disease and enables tumour progression. However, current therapies targeting COX-2 have an adverse safety profile owing to global prostanoid suppression. Thus, the search for therapies which more specifically modulate components of the PGE2 lifecycle has gained momentum. The prostanoid receptors, specifically the EP-series of receptors via which PGE2 exerts its effects, may be a particularly promising target as they sit at the initiating node of relevant signaling pathways. The enzymes regulating PGE2 synthesis and degradation may also represent potential targets. This article critically examines the literature regarding the PGE2-EP receptor axis and the prospect of targeting its components for anti-angiogenic therapy.