Metabolic rewiring of pancreatic ductal adenocarcinoma: New routes to follow within the maze.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a debilitating and almost universally fatal malignancy. Despite advances in understanding of the oncogenetics of the disease, very few clinical benefits have been shown. One of the main characteristics of PDAC is the tumor architecture where tumor cells are surrounded by a firm desmoplasia. By reducing vascularization, thus both oxygen and nutrients delivery to the tumor, this stroma causes the appearance of hypoxic zones driving metabolic adaptation in surviving tumor cells in order to cope with challenging conditions. This metabolic reprogramming promoted by environmental constraints enhances PDAC aggressiveness. In this review, we provide a brief overview of previous works regarding the importance of glucose and glutamine addiction of PDAC cells. In particular we aim to highlight the need for exploring the impact of metabolites other than glucose and glutamine, such as non-essential amino acids and oncometabolites, to find new treatments. We also discuss the need for progress in methodology for metabolites detection. The overall purpose of our review is to emphasize the need to look beyond what is currently known, with a focus on amino acid availability, in order to improve our understanding of PDAC biology.