Advances in prostaglandin E2 reprogramming pancreatic cancer microenvironment / 上海交通大学学报（医学版）

Pancreatic cancer is a highly malignant disease with poor prognosis. Accumulating evidences indicate that prostaglandin E2 (PGE2) can promote cancer progression by reprogramming tumor microenvironment (TME). On one hand, PGE2 can regulate immune cells, tumor cells, cancer-associated fibroblasts and endothelial cells in TME to boost growth, invasion and metastasis of pancreatic cancer. On the other hand, exosomes from tumor cells influence the synthesis, release and uptake of PGE2 and enhance its reprogramming abilities. Furthermore, PGE2 even plays an important role in the development of therapy resistance by stimulating tumor repopulation and inducing epithelial-mesenchymal transition. Hence, PGE2 might be a potential therapeutic target for intervention of pancreatic cancer.

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Platelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.