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

Targeting lactate metabolism for cancer therapeutics.

Author information

1
Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.

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.

PMID:
23999443
PMCID:
PMC3754272
DOI:
10.1172/JCI69741
[Indexed for MEDLINE]
Free PMC Article

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