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Science 295 (5559): 1526-1528

Copyright © 2002 by the American Association for the Advancement of Science

Effect of p53 Status on Tumor Response to Antiangiogenic Therapy

Joanne L. Yu,12 Janusz W. Rak,3 Brenda L. Coomber,4 Daniel J. Hicklin,5 Robert S. Kerbel12*

The p53 tumor suppressor gene is inactivated in the majority of human cancers. Tumor cells deficient in p53 display a diminished rate of apoptosis under hypoxic conditions, a circumstance that might reduce their reliance on vascular supply, and hence their responsiveness to antiangiogenic therapy. Here, we report that mice bearing tumors derived from p53-/- HCT116 human colorectal cancer cells were less responsive to antiangiogenic combination therapy than mice bearing isogenic p53+/+ tumors. Thus, although antiangiogenic therapy targets genetically stable endothelial cells in the tumor vasculature, genetic alterations that decrease the vascular dependence of tumor cells can influence the therapeutic response of tumors to this therapy.

1 Sunnybrook and Women's College Health Sciences Centre, Molecular and Cellular Biology Research, Room S-218, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.
2 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5S 1A1.
3 Hamilton Civic Hospitals Research Centre, McMaster University, Hamilton, Ontario, Canada L8V 1C3.
4 Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
5 ImClone Systems, Inc., 180 Varick Street, 7th Floor, New York, NY 10014, USA.
*   To whom correspondence should be addressed. E-mail: robert.kerbel{at}swchsc.on.ca

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