Targeting metabolic dependencies in pediatric cancer

Curr Opin Pediatr. 2020 Feb;32(1):26-34. doi: 10.1097/MOP.0000000000000853.

Abstract

Purpose of review: In an attempt to identify potential new therapeutic targets, efforts to describe the metabolic features unique to cancer cells are increasingly being reported. Although current standard of care regimens for several pediatric malignancies incorporate agents that target tumor metabolism, these drugs have been part of the therapeutic landscape for decades. More recent research has focused on the identification and targeting of new metabolic vulnerabilities in pediatric cancers. The purpose of this review is to describe the most recent translational findings in the metabolic targeting of pediatric malignancies.

Recent findings: Across multiple pediatric cancer types, dependencies on a number of key metabolic pathways have emerged through study of patient tissue samples and preclinical modeling. Among the potentially targetable vulnerabilities are glucose metabolism via glycolysis, oxidative phosphorylation, amino acid and polyamine metabolism, and NAD metabolism. Although few agents have yet to move forward into clinical trials for pediatric cancer patients, the robust and promising preclinical data that have been generated suggest that future clinical trials should rationally test metabolically targeted agents for relevant disease populations.

Summary: Recent advances in our understanding of the metabolic dependencies of pediatric cancers represent a source of potential new therapeutic opportunities for these diseases.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Amino Acids / metabolism
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Child
  • Folic Acid / metabolism
  • Glycolysis / drug effects
  • Glycolysis / physiology
  • Humans
  • Metabolic Networks and Pathways / drug effects*
  • Metabolic Networks and Pathways / physiology
  • Molecular Targeted Therapy* / methods
  • Molecular Targeted Therapy* / trends
  • NAD / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Oxidative Phosphorylation / drug effects
  • Polyamines / metabolism

Substances

  • Amino Acids
  • Antineoplastic Agents
  • Polyamines
  • NAD
  • Folic Acid