The pentose phosphate pathway and cancer

• The PPP is critical for cancer cell survival and ribonucleotide and lipid biosynthesis.
• Cancer cells modulate the PPP to maintain anabolic demands and redox homeostasis.
• Targeting the PPP for cancer therapy is challenging.
• Further studies on PPP regulation in cancer cells are required for targeting the PPP.

The pentose phosphate pathway (PPP), which branches from glycolysis at the first committed step of glucose metabolism, is required for the synthesis of ribonucleotides and is a major source of NADPH. NADPH is required for and consumed during fatty acid synthesis and the scavenging of reactive oxygen species (ROS). Therefore, the PPP plays a pivotal role in helping glycolytic cancer cells to meet their anabolic demands and combat oxidative stress. Recently, several neoplastic lesions were shown to have evolved to facilitate the flux of glucose into the PPP. This review summarizes the fundamental functions of the PPP, its regulation in cancer cells, and its importance in cancer cell metabolism and survival.