The Pentose Phosphate Pathway in Cancer: Regulation and Therapeutic Opportunities.

Nadine Darwiche, Noorhan Ghanem, Chirine El-Baba, Khaled Araji, Riyad El-Khoury, Julnar Usta

Journal: Chemotherapy 2022;66(5-6):179-191

PMID: 34775382

Full Text on S. Karger AG, Basel, Switzerland View on PubMed

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.

Address: Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.; Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon.

DOI: 10.1159/000519784

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https://doi.org/10.1159/000519784

MeSH Terms: Glucose, Glycolysis, Humans, Neoplasms, Oxidative Stress, Pentose Phosphate Pathway, Tumor Microenvironment