Targeting Lactate Metabolism for Cancer Therapeutics

J Clin Invest. 2013 Sep;123(9):3685-92. doi: 10.1172/JCI69741. Epub 2013 Sep 3.

Abstract

Lactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate mediates cancer cell intrinsic effects on metabolism and has additional non-tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, which induces metabolic reprogramming. Lactate also plays roles in promoting tumor inflammation and in functioning as a signaling molecule that stimulates tumor angiogenesis. Here we review the mechanisms of lactate production and transport and highlight emerging evidence indicating that targeting lactate metabolism is a promising approach for cancer therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biological Transport
  • Homeostasis
  • Humans
  • L-Lactate Dehydrogenase / antagonists & inhibitors
  • L-Lactate Dehydrogenase / metabolism
  • Lactic Acid / metabolism*
  • Molecular Targeted Therapy
  • Monocarboxylic Acid Transporters / antagonists & inhibitors
  • Monocarboxylic Acid Transporters / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • Monocarboxylic Acid Transporters
  • Lactic Acid
  • L-Lactate Dehydrogenase