Perspective: defects in cell cycle control and cancer.

The past several years have witnessed a dramatic accumulation of experimental and clinical evidence supporting the notion that the cell cycle machinery is commonly targeted on oncogenesis. While numerous cell cycle regulators qualify as proto-oncogenes or tumour suppressors and their aberrations may provide direct proliferative advantage to cancer cells, defects in checkpoint mechanisms act more indirectly yet affect both tumour progression and response to anticancer therapy. In this review, the ways that cell cycle defects contribute to oncogenesis are briefly illustrated and the emerging benefits of the newly gained insights into the cell cycle clock for clinical oncology are critically considered. Given the many reviews on the subject, emphasis is put on concepts rather than comprehensive treatment of the selected topics, with particular attention given to controversial issues, unorthodox phenomena, and the challenge facing the 'cell cycle and cancer field' at the transition to the next millennium.