Cell-cycle targeted therapies.
Eukaryotic organisms depend on an intricate and evolutionary conserved cell cycle to control cell division. The cell cycle is regulated by a number of important protein families which are common targets for mutational inactivation or overexpression in human tumours. The cyclin D and E families and their cyclin-dependent kinase partners initiate the phosphorylation of the retinoblastoma tumour suppressor protein and subsequent transition through the cell cycle. Cyclin/cdk activity and therefore control of cell division is restrained by two families of cyclin dependent kinase inhibitors. A greater understanding of the cell cycle has led to the development of a number of compounds with the potential to restore control of cell division in human cancers. This review will introduce the protein families that regulate the cell cycle, their aberrations in malignant progression and pharmacological strategies targeting this important process.
Swanton
Charles
C
Royal Marsden Hospital Breast Unit, Royal Marsden Hospital NHS Trust, London, UK. RobertCharles.Swanton@rmh.nthames.nhs.edu
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002986:Clinical Trials as Topic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005419:Flavonoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D019311:Staurosporine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; C054852:7-hydroxystaurosporine; D019311:Staurosporine