DNA topoisomerase I-targeted chemotherapy of human colon cancer in xenografts

B. C. Giovanella, J. S. Stehlin, M. E. Wall, M. C. Wani, A. W. Nicholas, Leroy-Fong Liu, R. Silber, M. Potmesil

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Abstract

Drug development is needed to improve chemotherapy of patients with locally advanced or metastratic colon carcinoma, who otherwise have an unfavorable prognosis. DNA topoisomerase I, a nuclear enzyme important for solving topological problems arising during DNA replication and for other cellular functions, has been identified as a principal target of a plant alkaliod 20(S)-camptothecin. Signficantly increased concentrations of this enzyme, compared to that in normal colonic mucosa, were found in advanced stages of human colon adenocarcinoma and in xenografts of colon cancer carried by immunodeficient mice. Several synthetic analogs of camptothecin, selected by tests with the purified enzyme and tissue-culture screens, were evaluated in the xenograft model. Unlike other anticancer drugs tested, 20(RS)-9-amino-camptothecin (9-AC) induced disease-free remissions. The overall drug toxicity was low and allowed for repeated courses of treatment.

Original languageEnglish
Pages (from-to)1046-1048
Number of pages3
JournalScience
Volume246
Issue number4933
Publication statusPublished - 1989
Externally publishedYes

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Cite this

Giovanella, B. C., Stehlin, J. S., Wall, M. E., Wani, M. C., Nicholas, A. W., Liu, L-F., Silber, R., & Potmesil, M. (1989). DNA topoisomerase I-targeted chemotherapy of human colon cancer in xenografts. Science, 246(4933), 1046-1048.