title: Molecular Pathways: Targeting Cellular Energy Metabolism in Cancer via Inhibition of SLC2A1 and LDHA.
abstract: Reprogramming of cellular energy metabolism is widely accepted to be one of the main hallmarks of cancer. The aberrant expression pattern of key regulators in the glycolysis pathway in cancer cells corroborates with the hypothesis that most cancer cells utilize aerobic glycolysis as their main ATP production method instead of mitochondrial oxidative phosphorylation. Overexpression of SLC2A1 and LDHA, both important regulators of the glycolysis pathway, was detected in the premalignant lesions and tumors of lung cancer patients, suggesting the involvement of these proteins in early carcinogenesis and tumor progression in cancer. Preclinical studies demonstrated that inhibiting SLC2A1 or LDHA led to diminished tumor growth in vitro and in vivo. SLC2A1 and LDHA inhibitors, when administered in combination with other chemotherapeutic agents, showed synergistic antitumor effects by resensitizing chemoresistant cancer cells to the chemotherapies. These results indicate that disrupting SLC2A1, LDHA, or other regulators in cancer cell energetics is a very promising approach for new targeted therapies.
authors.affiliation: Mattel Children's Hospital UCLA, Department of Pediatrics, UCLA, Los Angeles, California.
authors.forename: Aik T
authors.initials: AT
authors.lastname: Ooi
authors.affiliation: Mattel Children's Hospital UCLA, Department of Pediatrics, UCLA, Los Angeles, California. Pulmonary Medicine, UCLA, Los Angeles, California. Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California. Eli and Edythe Broad Stem Cell Research Center, UCLA, Los Angeles, California. bgomperts@mednet.ucla.edu.
authors.forename: Brigitte N
authors.initials: BN
authors.lastname: Gomperts
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D063646:Carcinogenesis / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D051272:Glucose Transporter Type 1; D007527:Isoenzymes; C495677:SLC2A1 protein, human; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1
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