title: Cyclin degradation for cancer therapy and chemoprevention.
abstract: Cancer is characterized by uncontrolled cell division resulting from multiple mutagenic events. Cancer chemoprevention strategies aim to inhibit or reverse these events using natural or synthetic pharmacologic agents. Ideally, this restores normal growth control mechanisms. Diverse classes of compounds have been identified with chemopreventive activity. What unites many of them is an ability to inhibit the cell cycle by specifically modulating key components. This delays division long enough for cells to respond to mutagenic damage. In some cases, damage is repaired and in others cellular damage is sufficient to trigger apoptosis. It is now known that pathways responsible for targeting G1 cyclins for proteasomal degradation can be engaged pharmacologically. Emergence of induced cyclin degradation as a target for cancer therapy and chemoprevention in pre-clinical models is discussed in this article. Evidence for cyclin D1 as a molecular pharmacologic target and biological marker for clinical response is based on experience of proof of principle trials.
authors.affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. sarah.freemantle@dartmouth.edu
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Freemantle
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Feng
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Galimberti
authors.forename: Steven
authors.initials: S
authors.lastname: Blumen
authors.forename: David
authors.initials: D
authors.lastname: Sekula
authors.forename: Sutisak
authors.initials: S
authors.lastname: Kitareewan
authors.forename: Konstantin H
authors.initials: KH
authors.lastname: Dragnev
authors.forename: Ethan
authors.initials: E
authors.lastname: Dmitrovsky
mesh_terms: D002453:Cell Cycle; D019938:Cyclin D1 / Q000378:metabolism; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism
chemical_list: C534702:CCNG1 protein, human; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D019938:Cyclin D1; D046988:Proteasome Endopeptidase Complex