dc.contributor.author |
Chan, DA |
en |
dc.contributor.author |
Sutphin, PD |
en |
dc.contributor.author |
Nguyen, P |
en |
dc.contributor.author |
Turcotte, S |
en |
dc.contributor.author |
Lai, EW |
en |
dc.contributor.author |
Banh, A |
en |
dc.contributor.author |
Reynolds, GE |
en |
dc.contributor.author |
Chi, JT |
en |
dc.contributor.author |
Wu, J |
en |
dc.contributor.author |
Solow-Cordero, DE |
en |
dc.contributor.author |
Bonnet, Muriel |
en |
dc.contributor.author |
Flanagan, Jack |
en |
dc.contributor.author |
Bouley, DM |
en |
dc.contributor.author |
Graves, EE |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Hay, Michael |
en |
dc.contributor.author |
Giaccia, AJ |
en |
dc.date.accessioned |
2011-11-18T02:17:25Z |
en |
dc.date.issued |
2011-08-03 |
en |
dc.identifier.citation |
Science Translational Medicine 3(94):1-9 Article number 94ra70 03 Aug 2011 |
en |
dc.identifier.issn |
1946-6234 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/9391 |
en |
dc.description.abstract |
Identifying new targeted therapies that kill tumor cells while sparing normal tissue is a major challenge of cancer research. Using a high-throughput chemical synthetic lethal screen, we sought to identify compounds that exploit the loss of the von Hippel–Lindau (VHL) tumor suppressor gene, which occurs in about 80% of renal cell carcinomas (RCCs). RCCs, like many other cancers, are dependent on aerobic glycolysis for ATP production, a phenomenon known as the Warburg effect. The dependence of RCCs on glycolysis is in part a result of induction of glucose transporter 1 (GLUT1). Here, we report the identification of a class of compounds, the 3-series, exemplified by STF-31, which selectively kills RCCs by specifically targeting glucose uptake through GLUT1 and exploiting the unique dependence of these cells on GLUT1 for survival. Treatment with these agents inhibits the growth of RCCs by binding GLUT1 directly and impeding glucose uptake in vivo without toxicity to normal tissue. Activity of STF-31 in these experimental renal tumors can be monitored by [18F]fluorodeoxyglucose uptake by micro–positron emission tomography imaging, and therefore, these agents may be readily tested clinically in human tumors. Our results show that the Warburg effect confers distinct characteristics on tumor cells that can be selectively targeted for therapy. |
en |
dc.language |
EN |
en |
dc.publisher |
American Association for the Advancement of Science |
en |
dc.relation.ispartofseries |
Science Translational Medicine |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from
http://www.sherpa.ac.uk/romeo/issn/1946-6234/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
DEFICIENCY SYNDROME |
en |
dc.subject |
CANCER CELLS |
en |
dc.subject |
HYPOXIA |
en |
dc.subject |
GLUCOSE |
en |
dc.subject |
GENE |
en |
dc.subject |
ADAPTATION |
en |
dc.subject |
EXPRESSION |
en |
dc.subject |
INHIBITOR |
en |
dc.subject |
BINDING |
en |
dc.subject |
DEATH |
en |
dc.title |
Targeting GLUT1 and the Warburg Effect in Renal Cell Carcinoma by Chemical Synthetic Lethality |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1126/scitranslmed.3002394 |
en |
pubs.issue |
94 |
en |
pubs.begin-page |
1 |
en |
pubs.volume |
3 |
en |
dc.rights.holder |
Copyright: American Association for the Advancement of Science |
en |
dc.identifier.pmid |
21813754 |
en |
pubs.end-page |
9 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
221772 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Pharmacology |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.number |
94ra70 |
en |
pubs.record-created-at-source-date |
2011-11-18 |
en |
pubs.dimensions-id |
21813754 |
en |