Cell-cycle Arrest Versus Cell Death in Cancer Therapy

Nat Med. 1997 Sep;3(9):1034-6. doi: 10.1038/nm0997-1034.

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 checkpoints. 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 gamma-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Cycle / radiation effects*
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Death / radiation effects*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / radiotherapy
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Gamma Rays
  • Genes, p53
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / radiotherapy*
  • Radiation Tolerance / genetics
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

Substances

  • Antineoplastic Agents
  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins