An intermittent approach for cancer chemoprevention

Nat Rev Cancer. 2011 Nov 10;11(12):879-85. doi: 10.1038/nrc3167.


Cancer chemoprevention approaches generally use long-term, continuous treatment, which can produce major preventive effects but which can also have unexpected serious adverse events. This raises the question of whether intermittent dosing schedules might reduce toxicity while retaining benefit, a concept that we call short-term intermittent therapy to eliminate premalignancy (SITEP). Recent preclinical studies support a novel SITEP approach whereby short-term, intermittent therapy eliminates premalignant cells via apoptosis that is induced by synthetic lethal interactions. Synthetic lethality allows personalized, selective elimination of premalignant clones without harming normal cells. This Opinion article provides a detailed discussion of the principle, method and future development of the SITEP approach.

Publication types

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

MeSH terms

  • Animals
  • Chemoprevention*
  • Genes, APC
  • Humans
  • Mice
  • Neoplasms / etiology
  • Neoplasms / genetics
  • Neoplasms / prevention & control*
  • Precancerous Conditions / drug therapy*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Sulindac / therapeutic use
  • TNF-Related Apoptosis-Inducing Ligand / therapeutic use
  • ras Proteins / genetics


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Sulindac
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins