title: Hereditary cancer syndromes as model systems for chemopreventive agent development.
abstract: Research in chemoprevention has undergone a shift in emphasis for pragmatic reasons from large, phase III randomized studies to earlier phase studies focused on safety, mechanisms, and utilization of surrogate endpoints such as biomarkers instead of cancer incidence. This transition permits trials to be conducted in smaller populations and at substantially reduced costs while still yielding valuable information. This article will summarize some of the current chemoprevention challenges and the justification for the use of animal models to facilitate identification and testing of chemopreventive agents as illustrated though four inherited cancer syndromes. Preclinical models of inherited cancer syndromes serve as prototypical systems in which chemopreventive agents can be developed for ultimate application to both the sporadic and inherited cancer settings.
authors.affiliation: National Institutes of Health, National Cancer Institute, Division of Cancer Prevention, Bethesda, MD, USA. Electronic address: Farzana.walcott@nih.gov.
authors.forename: Farzana L
authors.initials: FL
authors.lastname: Walcott
authors.affiliation: National Institutes of Health, National Cancer Institute, Division of Cancer Prevention, Bethesda, MD, USA.
authors.forename: Jigar
authors.initials: J
authors.lastname: Patel
authors.affiliation: Consultant to National Institutes of Health, National Cancer Institute, Division of Cancer Prevention, Chemopreventive Agent Development Research Group, Bethesda, MD, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Lubet
authors.affiliation: National Institutes of Health, National Cancer Institute, Division of Cancer Prevention, Gastrointestinal & Other Cancers Research, Bethesda, MD, USA.
authors.forename: Luz
authors.initials: L
authors.lastname: Rodriguez
authors.affiliation: National Institutes of Health, National Cancer Institute, Center for Cancer Research, Genetics Branch, Bethesda, MD, USA. Electronic address: calzonek@mail.nih.gov.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Calzone
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000517:prevention & control*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D018890:Chemoprevention; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000517:prevention & control*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D055808:Drug Discovery; D005260:Female; D017491:Genes, APC; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D016864:Li-Fraumeni Syndrome / Q000235:genetics / Q000517:prevention & control*; D008687:Metformin / Q000627:therapeutic use; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D019683:Penetrance; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D007004:Hypoglycemic Agents; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D020845:Selective Estrogen Receptor Modulators; D016159:Tumor Suppressor Protein p53; D008687:Metformin; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes; D001241:Aspirin
keywords: Chemoprevention; HBOC; Hereditary cancer; Li-Fraumeni syndrome; Lynch syndrome