PARP and other prospective targets for poisoning cancer cell metabolism

Judith Michels, Florine Obrist, Maria Castedo, Ilio Vitale, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

Abstract

Increasing evidence indicates that cancer cells rewire their metabolism during tumorigenesis. The high intracellular levels of lactate and reactive oxygen species (ROS) generated during enhanced aerobic glycolysis and mitochondrial oxidative phosphorylation respectively led to oxidative stress. The detoxification of these accumulating metabolites and the equilibrium between reduced and oxidized nicotine adenine dinucleotide (NADH and NAD+) are two prominent mechanisms regulating redox status and hence energy homeostasis in tumors. Targeting both processes may thus be selectively cytotoxic for cancer cells. In this context, the impact of poly(ADP-ribose) polymerase (PARP) inhibitors, a class of anticancer agents employed for the treatment of DNA repair deficient tumors, on energy homeostasis and mitochondrial respiration regulation has potential clinical implications. Here we provide an overview of the metabolic reprogramming occurring in cancer cells and discuss the translational perspectives of targeting tumor metabolism and redox balance for antineoplastic therapy.

Original languageEnglish
Pages (from-to)164-171
Number of pages8
JournalBiochemical Pharmacology
Volume92
Issue number1
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • Autophagy
  • Mitochondria
  • NADPH
  • PARP-1
  • Sirtuin

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry
  • Medicine(all)

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