Macro understanding of the therapeutic role of phospholipase and their metabolites in pancreatic ductal and periampullary adenocarcinoma

Pancreatic cancer (PanCa) is one of the most severe types of cancer and the leading cause of cancer-associated deaths. At present, it is extremely difficult to prevent or diagnose the ailment at a curable stage, as the symptoms are not clear until late stage of the disease and lack of specific markers, which might assist in early detection. Moreover, the existing conventional treatment protocol helps only little in the disease management due to the extreme heterogeneous metabolic rewiring, impenetrable stroma, and vague mechanism of disease progression associated with carcinoma of the pancreas. Also, the new trend of small molecules used in targeted anticancer therapy showed insignificant benefit and was unable to make any difference in overall survival. Thus, there is a need to explore novel approaches by apposite understanding of the complicated biology of the disease to find innovative targets. Phospholipases, the crucial regulators of cellular signaling through lipid metabolism, engenders a vast range of lipid mediators, which intricately control numerous imperative metabolic pathways linked with cell proliferation, apoptosis, cell migration, inflammation, invasion, metastasis, and angiogenesis, all of which are indispensable for PanCa. Here, in this chapter, we summarize the association of PanCa with phospholipases for a detailed understanding of metabolism of phospholipids, associated enzymes, and phospholipases that would enable us to develop new drug targets and novel therapeutic approaches for better management of PanCa.