Cyclooxygenases in pancreatic ductal adenocarcinoma: are they inflammatory catalysts for tumor growth.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers with a relative 5-year survival around 12%. One of the greatest challenges in PDAC is the frequent systemic dissemination at the time of diagnosis and the dense, fibrotic extracellular matrix that prevents chemotherapeutics and cytotoxic immune cells from entering the tumor stroma. The cyclooxygenase (COX) enzymes and their downstream molecular products play important roles in cancer development and dissemination. The COX isoenzymes are overexpressed in many cancers and inhibition of the COX-2 isoform, and the use of acetylsalicylic acid has recently been demonstrated to reduce cancer recurrence after surgery in subgroups of patients with certain molecular subtypes, such as PI3K mutations, overexpression of vascular growth factors, etc.). COX-2-related pathways are involved in suppressing tumor immunity and promoting stem cell-like properties of cancer cells. Especially in PDAC, targeting the COX enzymes might be of importance in subgroups or as an adjunct as COX-2 is frequently overexpressed and associated with a worse prognosis. Selective COX-2 inhibitors have been demonstrated to reduce tumor growth, invasiveness, and metastasis formation in preclinical trials. This review evaluates existing preclinical and clinical studies investigating the potential for targeting the COX enzymes in PDAC treatment.