The therapeutic potential of targeting the cell cycle.
With the advent of modern molecular genetics, molecular biology and biochemistry has come a revolution in oncology drug discovery research. We are rapidly developing an increased understanding in the mechanisms driving cellular proliferation, transformation, differentiation and metastasis. The hope is that from these advances will emerge novel therapeutics that are more specific, more efficacious and less toxic than their predecessors. Uncontrolled proliferation is a hallmark of a cancer cell. Over the past two decades it has become increasingly clear that molecules that directly control cell cycle progression accumulate defects during tumourigenesis. These defects can result in the loss of checkpoint control and/or the inappropriate activation of the 'drivers' of cell cycle progression, the cyclin-dependent kinases (cdks). This review will describe the recent advances in our understanding of cell cycle regulation and its relation to tumourigenesis, and highlight the potential for the development of novel anticancer therapeutics.
Webster
K R
KR
Department of Oncology Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. websterk@bms.com