Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality

Science Translational Medicine

Volumn 3, Issue 94, 2011, Pages

  Chan, Denise A ^a,b   Sutphin, Patrick D ^c   Nguyen, Phuong ^a   Turcotte, Sandra ^d   Lai, Edwin W ^a   Banh, Alice ^a   Reynolds, Gloria E ^b   Chi, Jen Tsan ^e   Wu, Jason ^a   Solow Cordero, David E ^a   Bonnet, Muriel ^f   Flanagan, Jack U ^f   Bouley, Donna M ^a   Graves, Edward E ^a   Denny, William A ^f   Hay, Michael P ^f   Giaccia, Amato J ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d UNIVERSITÉ DE MONCTON   (Canada)

^e DUKE UNIVERSITY MEDICAL CENTER   (United States)

^f UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE PHOSPHATE; ANTINEOPLASTIC AGENT; FLUORODEOXYGLUCOSE F 18; GLUCOSE; GLUCOSE TRANSPORTER 1; HYPOXIA INDUCIBLE FACTOR; LACTIC ACID; STF 31; UNCLASSIFIED DRUG; VON HIPPEL LINDAU PROTEIN; ADENOSINE TRIPHOSPHATE; SLC2A1 PROTEIN, HUMAN;

ANAEROBIC GLYCOLYSIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER CELL DESTRUCTION; CANCER INHIBITION; CELL SURVIVAL; CONTROLLED STUDY; DNA DAMAGE; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG MECHANISM; DRUG PROTEIN BINDING; ENZYME SYNTHESIS; GENE OVEREXPRESSION; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; HUMAN; HUMAN CELL; IN VIVO STUDY; KIDNEY CARCINOMA; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN TARGETING; BIOSYNTHESIS; CHEMISTRY; GLYCOLYSIS; KIDNEY TUMOR; METABOLISM;

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENTS; APOPTOSIS; CARCINOMA, RENAL CELL; GLUCOSE; GLUCOSE TRANSPORTER TYPE 1; GLYCOLYSIS; HUMANS; KIDNEY NEOPLASMS;

EID: 79961215490     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3002394     Document Type: Article

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30. Acknowledgments: We thank G. Thomas for ACHN cells and G.-O. Ahn, A. Krieg, and I. Papandreou for technical assistance. Funding: This investigation was supported by grants from the Action to Cure Kidney Cancer/Cecile and Ken Youner Fund for Cancer Research, the Association for International Cancer Research 10-0042 (M.B.), the Maurice Wilkins Centre for Biodiscovery (M.P.H. and J.U.F.), the Skippy Frank Translational Medicine and Life Sciences Fund (A.J.G.), the Silicon Valley Foundation (A.J.G.), National Cancer Institute (NCI)-CA-123823 (D.A.C.), NCI-T32-CA-121940 (E.W.L.), NCI-CA-67166 (A.J.G.), and NCI-CA-082566 (M.P.H. and A.J.G.). Author contributions: D.A.C., P.D.S., P.N., S.T., E.W.L., D.E.S.-C., M.P.H., and A.J.G. designed the experiments. D.A.C., P.D.S., P.N., S.T., E.W.L., A.B., G.E.R., M.B., J.U.F., M.P.H., and A.J.G. performed the experiments and analyzed the data. J.-T.C. performed the microarray analyses. J.W. and D.E.S.-C. assisted and provided technical advice for the high-throughput screening. Modeling was performed by J.U.F. D.M.B. contributed to the in vivo toxicity studies. E.E.G. provided technical advice and analysis of the imaging studies. D.A.C., W.A.D., M.P.H., and A.J.G. supervised these studies. D.A.C. and A.J.G. wrote most of the article. Competing interests: Stanford University holds a patent "Preparation of heteroaryl benzamides useful in treating diseases" PCT Int. Appl. WO 2011011514, which is related to the work described in this paper, with P.D.S., S.T., D.A.C., W.A.D., M.P.H., and A.J.G. named as inventors. A.J.G. is a founder of and D.A.C. is a scientific consultant for Ruga, a company that discovers and develops targeted therapeutics in oncology and has licensed this patent. Drugs used in these studies are available from the author.