title: An intermittent approach for cancer chemoprevention.
abstract: 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.
authors.affiliation: Departments of Clinical Cancer Prevention, and Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. xwwu@mdanderson.org
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Wu
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D000818:Animals; D018890:Chemoprevention; D017491:Genes, APC; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000188:drug therapy*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D013467:Sulindac / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000627:therapeutic use; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D013467:Sulindac; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
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