Hereditary Cancer Syndromes as Model Systems for Chemopreventive Agent Development

• Published in: Seminars in oncology Vol. 43; no. 1; pp. 134 - 145
• Main Authors: Walcott, Farzana L., MD, MPH, Patel, Jigar, MD, Lubet, Ronald, PhD, Rodriguez, Luz, MD, Calzone, Kathleen A., PhD, RN, APNG, FAAN
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2016
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adenomatous Polyposis Coli - genetics; Adenomatous Polyposis Coli - prevention & control; Adenosine Triphosphatases - metabolism; Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Anticarcinogenic Agents - pharmacology; Anticarcinogenic Agents - therapeutic use; Aspirin - therapeutic use; Chemoprevention; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - prevention & control; Cyclooxygenase 2 Inhibitors - therapeutic use; Disease Models, Animal; DNA Repair Enzymes - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug Discovery; Female; Genes, APC; Genes, BRCA1; Genes, BRCA2; HBOC; Hematology, Oncology and Palliative Medicine; Hereditary Breast and Ovarian Cancer Syndrome - genetics; Hereditary Breast and Ovarian Cancer Syndrome - prevention & control; Hereditary cancer; Humans; Hypoglycemic Agents - therapeutic use; Li-Fraumeni syndrome; Li-Fraumeni Syndrome - genetics; Li-Fraumeni Syndrome - prevention & control; Lynch syndrome; Metformin - therapeutic use; Mismatch Repair Endonuclease PMS2; Mutation; MutL Protein Homolog 1; MutS Homolog 2 Protein - genetics; Nuclear Proteins - genetics; Penetrance; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; Selective Estrogen Receptor Modulators - therapeutic use; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Hereditary cancer; Chemoprevention; Lynch syndrome; Li-Fraumeni syndrome; HBOC
• ISSN: 0093-7754; 1532-8708
• DOI: 10.1053/j.seminoncol.2015.09.015

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