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Combinatorial chemoprevention of intestinal neoplasia

Nature Medicine volume 6, pages 1024–1028 (2000)Cite this article

Abstract

A combination of two drugs afforded remarkable protection from intestinal neoplasia in APCMin/+ mice, a murine model of human familial adenomatous polyposis (FAP). One of the drugs was sulindac, a prototypical non-steroidal anti-inflammatory drug with established chemopreventative activity. The second drug was EKI-569, a newly developed, irreversible inhibitor of the epidermal growth factor receptor kinase. Although 100% of the untreated APCMin/+ mice developed ∼20 polyps, nearly half the mice treated with these two agents developed no polyps at all. These results suggest a powerful strategy for the chemoprevention of human colonic neoplasia.

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Figure 1
Figure 2
Figure 3: Binding of EKB-569 to EGFR a, Total protein (non-IP 50 μg, ▴) or protein immunoprecipitated with an EGFR antibody (IP 200 μg, ♦) from HN5 membranes incubated with [14C]-EKB-569.

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Acknowledgements

This work was supported by the Clayton Fund, National Institutes of Health grants CA 57345 and CA 62924, and Wyeth-Ayerst Research.

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Authors and Affiliations

  1. The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, Maryland, 21231, Baltimore, USA

    Christopher J. Torrance, Peta E. Jackson, Kenneth W. Kinzler & Bert Vogelstein

  2. School of Hygiene and Public Health, Johns Hopkins University, Baltimore, 21205, Maryland, USA

    Peta E. Jackson

  3. Department of Pathology, Johns Hopkins University, Baltimore, 21205, Maryland, USA

    Elizabeth Montgomery

  4. Chemical Sciences, Wyeth-Ayerst Research, Pearl River, 10965, New York, USA

    Allan Wissner

  5. Oncology and Immunoinflammatory Research, Pearl River, 10965, New York, USA

    Maria Nunes, Philip Frost & Carolyn M. Discafani

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Correspondence to Philip Frost.

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Torrance, C., Jackson, P., Montgomery, E. et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med 6, 1024–1028 (2000). https://doi.org/10.1038/79534

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