Cell-cycle arrest versus cell death in cancer therapy

Todd Waldman, Yonggang Zhang, Larry Dillehay, Jian Yu, Kenneth Kinzler, Bert Vogelstein, Jerry Williams

Research output: Contribution to journalArticle

Abstract

In response to anticancer therapeutics, human colon cancer cells growing in vitro either enter into a stable arrest or die, depending on the integrity of their cell-cycle checkpoints1. To test whether altered checkpoints can modulate sensitivity to treatment in vivo, xenografts were established from isogenic lines differing only in their p21 checkpoint status. Although all tumors with intact checkpoint function underwent regrowth after treatment with γ-radiation, a significant fraction of checkpoint-deficient tumors were completely cured. This difference in sensitivity was not detected by the clonogenic survival assay, because both arrest and death preclude outgrowth of colonies. These results demonstrate that checkpoint status affects sensitivity to anticancer treatments in vivo, and these findings have important implications for identifying and testing new therapeutic compounds.

Original languageEnglish (US)
Pages (from-to)1034-1036
Number of pages3
JournalNature medicine
Volume3
Issue number9
DOIs
StatePublished - Sep 1 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Waldman, T., Zhang, Y., Dillehay, L., Yu, J., Kinzler, K., Vogelstein, B., & Williams, J. (1997). Cell-cycle arrest versus cell death in cancer therapy. Nature medicine, 3(9), 1034-1036. https://doi.org/10.1038/nm0997-1034