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Experimental Therapeutics, Molecular Targets, and Chemical Biology

Molecular Pharmacology of Cancer Therapy in Human Colorectal Cancer by Gene Expression Profiling

Paul A. Clarke, Mark L. George, Sandra Easdale, David Cunningham, R. Ian Swift, Mark E. Hill, Diana M. Tait and Paul Workman
Paul A. Clarke
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Mark L. George
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Sandra Easdale
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David Cunningham
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R. Ian Swift
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Mark E. Hill
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Diana M. Tait
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Paul Workman
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DOI:  Published October 2003
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Abstract

Global gene expression profiling has potential for elucidating the complex cellular effects and mechanisms of action of novel targeted anticancer agents or existing chemotherapeutics for which the precise molecular mechanism of action may be unclear. In this study, decreased expression of genes required for RNA and protein synthesis, and for metabolism were detected in rectal cancer biopsies taken from patients during a 5-fluorouracil infusion. Our observations demonstrate that this approach is feasible and can detect responses that may have otherwise been missed by conventional methods. The results suggested new mechanism-based combination treatments for colorectal cancer and demonstrated that expression profiling could provide valuable information on the molecular pharmacology of established and novel drugs.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • ↵1 Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org).

  • ↵2 Supported by Cancer Research UK (to P. C. and P. W.; grant number SP2330, and P. W. is a Cancer Research UK Life Fellow). S. E. is supported by a Cancer Research UK Studentship.

  • ↵3 To whom requests for reprints should be addressed, at Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom. Phone: 44-020-8722-4131; Fax: 44-020-8770-7899; E-mail: Paul.Clarke{at}icr.ac.uk

  • Received March 13, 2003.
  • Revision received July 14, 2003.
  • Accepted July 29, 2003.
  • ©2003 American Association for Cancer Research.
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Cancer Research: 63 (20)
October 2003
Volume 63, Issue 20
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Molecular Pharmacology of Cancer Therapy in Human Colorectal Cancer by Gene Expression Profiling
Paul A. Clarke, Mark L. George, Sandra Easdale, David Cunningham, R. Ian Swift, Mark E. Hill, Diana M. Tait and Paul Workman
Cancer Res October 15 2003 (63) (20) 6855-6863;

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Molecular Pharmacology of Cancer Therapy in Human Colorectal Cancer by Gene Expression Profiling
Paul A. Clarke, Mark L. George, Sandra Easdale, David Cunningham, R. Ian Swift, Mark E. Hill, Diana M. Tait and Paul Workman
Cancer Res October 15 2003 (63) (20) 6855-6863;
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