In cancer, all roads lead to NADPH

Gulam Mohmad Rather, Alvinsyah Adhityo Pramono, Zoltan Szekely, Joseph R. Bertino, Philip Michael Tedeschi

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

Cancer cells require increased levels of NADPH for increased nucleotide synthesis and for protection from ROS. Recent studies show that increased NADPH is generated in several ways. Activated AKT phosphorylates NAD kinase (NADK), increasing its activity. NADP formed, is rapidly converted to NADPH by glucose 6-phosphate dehydrogenase and malic enzymes, overexpressed in tumor cells with mutant p53. Calmodulin, overexpressed in some cancers, also increases NADK activity. Also, in IDH1/2 mutant cancer, NADPH serves as the cofactor to generate D-2 hydroxyglutarate, an oncometabolite. The requirement of cancer cells for elevated levels of NADPH provides an opportunity to target its synthesis for cancer treatment.

Original languageEnglish (US)
Article number107864
JournalPharmacology and Therapeutics
Volume226
DOIs
StatePublished - Oct 2021

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Keywords

  • Calmodulin
  • NAD
  • NAD kinase
  • NADPH
  • ROS

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