The Pentose Phosphate Pathway in Cancer: Regulation and Therapeutic Opportunities

Chemotherapy. 2021;66(5-6):179-191. doi: 10.1159/000519784. Epub 2021 Nov 12.

Abstract

Background: Tumorigenesis is associated with deregulation of nutritional requirements, intermediary metabolites production, and microenvironment interactions. Unlike their normal cell counterparts, tumor cells rely on aerobic glycolysis, through the Warburg effect.

Summary: The pentose phosphate pathway (PPP) is a major glucose metabolic shunt that is upregulated in cancer cells. The PPP comprises an oxidative and a nonoxidative phase and is essential for nucleotide synthesis of rapidly dividing cells. The PPP also generates nicotinamide adenine dinucleotide phosphate, which is required for reductive metabolism and to counteract oxidative stress in tumor cells. This article reviews the regulation of the PPP and discusses inhibitors that target its main pathways. Key Message: Exploiting the metabolic vulnerability of the PPP offers potential novel therapeutic opportunities and improves patients' response to cancer therapy.

Keywords: Cancer; Metabolism; Pentose phosphate pathway.

Publication types

  • Review

MeSH terms

  • Glucose
  • Glycolysis
  • Humans
  • Neoplasms* / drug therapy
  • Oxidative Stress
  • Pentose Phosphate Pathway*
  • Tumor Microenvironment

Substances

  • Glucose