Radiosensitization of prostate cancer by priming the wild-type p53-dependent cellular senescence pathway

Cancer Biol Ther. 2007 Aug;6(8):1165-70. doi: 10.4161/cbt.6.8.4544. Epub 2007 Aug 5.

Abstract

A dramatic stage-migration in diagnosis of prostate cancer has led to earlier detection of clinically localized carcinoma and an increased use of radiation therapy. The p53 protein responds to irradiation-induced DNA damage by removing critically damaged cells from the proliferative pool. This review will focus on the dominant role that p53-dependent cellular senescence, rather than cell death, plays in determining the radiosensitivity of human prostate cancer cells in vitro. The finding that senescence is a primary mechanism of tumor regression indicates that p53 activators or downstream effectors may prove effective in radiosensitizing some carcinoma of the prostate.

Keywords: Akt; MDM2; PTEN; nutlin; p53; prostate cancer; radiosensitization; senescence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / physiology
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cellular Senescence / physiology
  • Cellular Senescence / radiation effects*
  • DNA Damage
  • Humans
  • Male
  • Models, Biological
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology
  • Prostatic Neoplasms / radiotherapy*
  • Signal Transduction / physiology
  • Signal Transduction / radiation effects*
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Tumor Suppressor Protein p53