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The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer

Authors

  • Katrien Vermeulen,

    1. Faculty of Medicine, Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium
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  • Dirk R. Van Bockstaele,

    1. Faculty of Medicine, Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium
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  • Zwi N. Berneman

    Corresponding author
    1. Faculty of Medicine, Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium
      Zwi N. Berneman, Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium. Tel.: +32 3821 37 80; Fax: +32 3821 42 86; E-mail: zwi.berneman@uza.be
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Zwi N. Berneman, Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium. Tel.: +32 3821 37 80; Fax: +32 3821 42 86; E-mail: zwi.berneman@uza.be

Abstract

Abstract.  The cell cycle is controlled by numerous mechanisms ensuring correct cell division. This review will focus on these mechanisms, i.e. regulation of cyclin-dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events. The quality checkpoints activated after DNA damage are also discussed. The complexity of the regulation of the cell cycle is also reflected in the different alterations leading to aberrant cell proliferation and development of cancer. Consequently, targeting the cell cycle in general and CDK in particular presents unique opportunities for drug discovery. This review provides an overview of deregulation of the cell cycle in cancer. Different families of known CDK inhibitors acting by ATP competition are also discussed. Currently, at least three compounds with CDK inhibitory activity (flavopiridol, UCN-01, roscovitine) have entered clinical trials.

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