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      Targeting lactate metabolism for cancer therapeutics.

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          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.

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          Author and article information

          Journal
          J Clin Invest
          The Journal of clinical investigation
          American Society for Clinical Investigation
          1558-8238
          0021-9738
          Sep 2013
          : 123
          : 9
          Affiliations
          [1 ] Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
          Article
          69741
          10.1172/JCI69741
          3754272
          23999443
          95cf8387-353a-4c53-a552-cfa95770d9cf
          History

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