DNA damage is able to induce senescence in tumor cells in vitro and in vivo

Cancer Res. 2002 Mar 15;62(6):1876-83.


Often the use of cytotoxic drugs in cancer therapy results in stable disease rather than regression of the tumor, and this is typically seen as a failure of treatment. We now show that DNA damage is able to induce senescence in tumor cells expressing wild-type p53. We also show that cytotoxics are capable of inducing senescence in tumor tissue in vivo. Our results suggest that p53 and p21 play a central role in the onset of senescence, whereas p16(INK4a) function may be involved in maintaining senescence. Thus, like apoptosis, senescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Cell Cycle / drug effects
  • Cellular Senescence / drug effects
  • Cellular Senescence / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis
  • DNA Damage / physiology*
  • Etoposide / pharmacology
  • Humans
  • Irinotecan
  • Neoadjuvant Therapy
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / physiology
  • beta-Galactosidase / metabolism


  • Antineoplastic Agents, Phytogenic
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Suppressor Protein p53
  • Etoposide
  • Irinotecan
  • beta-Galactosidase
  • Camptothecin