Open AccessThe Pentose Phosphate Pathway in Cancer: Regulation and Therapeutic Opportunities
Author(s) -
Noorhan Ghanem,
Chirine El-Baba,
Khaled Araji,
Riyad El-Khoury,
Jinan Usta,
Nadine Darwiche
Publication year - 2021
Publication title -
chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.539
H-Index - 54
eISSN - 1421-9794
pISSN - 0009-3157
DOI - 10.1159/000519784
Subject(s) - pentose phosphate pathway , nicotinamide adenine dinucleotide phosphate , glycolysis , carcinogenesis , metabolic pathway , nad+ kinase , biochemistry , cancer cell , anaerobic glycolysis , oxidative phosphorylation , biology , metabolism , nicotinamide adenine dinucleotide , warburg effect , microbiology and biotechnology , cancer research , chemistry , cancer , enzyme , oxidase test , genetics , gene
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.